Table 1.

Defining Histological Signs of Intestine Presentations as Observed Within Zebrafish Submitted to the Zebrafish International Resource Center Diagnostic Service 2000–2012

Intestinal presentation	Defining signs
Normal intestine	One cell thick layer of columnar epithelial cells lining mucosal folds with basally-oriented oval nuclei; mucosal folds become progressively shorter caudally, causing “villi” (the normal undulating structure of the intestinal wall appears villous, but lacks the true anatomic characteristics of villi) to appear shorter as the intestine approaches the excretory vent (anus); lamina propria, but no submucosa; inner circular and outer longitudinal smooth muscle layers invest the intestine throughout its length. Mucosal mucus (goblet) cells can be observed and increase in number distally.
Hyperplastic intestine	Multilayered and increased numbers of epithelial cells, especially within basilar mucosal folds; “piling-up” of mucosal epithelial cells; nuclear pseudostratification; enhanced nuclear basophilia; pseudocrypt formation resulting from increased mucosal folding; anisokaryosis frequently observed and increased mitotic figures.
Dysplastic intestine	Features of hyperplastic intestine in addition to increased nuclear and cellular pleomorphism, and occasionally aberrant mitotic figures, the loss of nuclear polarity and disorganization or absence of pre-existing histoanatomic architecture.
Intestinal adenocarcinoma	Features of dysplastic intestine plus formation of disorganized pseudocrypts with invasion deep into the lamina propria and frequently through the basement membrane into the underlying muscularis layers; bizarre mitotic figures; neoplastic epithelial cells are pleomorphic and may be columnar, cuboidal or attenuated; hyperchromatic nuclei; annular strictures and fibroplasia frequently accompany tumorigenesis; pseudocrypts formed by the folding of neoplastic mucosal epithelium often resembled pseudoacinar structures that contained intraluminal sloughed rafts of necrotic neoplastic cells.
Intestinal small cell carcinoma/carcinoid-like tumor	Sheets and nests of round, polygonal or fusiform cells with minimal cytoplasm; hyperchromatic nuclei with granular chromatin and inconspicuous nucleoli; extensive fibroplasia; tumor cells occasionally formed an insular or organoid pattern characteristic of neuroendocrine tumors.
Intestinal tubular/tubulovillous adenoma	Focal adenomatous polypoid structures with clusters of proprial pseudocrypts resembling mammalian glandular colonic crypts. The pseudocrypts often are lined by hyperplastic mucosal epithelium where the cells are crowded and have hyperchromatic nuclei. Increased mitotic figures are observed. Tubulovillous adenoma is essentially similar to tubular adenoma with a combination of both villous and pseudocrypt structures.