Answer: High grade dysplasia

Histology: The diagnosis in this case is Barrett’s esophagus with high-grade dysplasia. There are closely packed, small, irregular glands with both the crypt and surface epithelium showing markedly atypical, stratified hyperchromatic nuclei with nucleoli. Several mitotic figures are present. There is no evidence of necrosis, cribiforming of glands, individual cell infiltration or desmoplasia. Rare intraepithelial neutrophils are present. Image 2 shows evidence of pseudo-regression characterized by low grade dysplastic columnar epithelium superficially covered by reactive squamous mucosa.

Discussion: Barrett’s esophagus is any type of gastric columnar mucosa with or without intestinal metaplasia, extending into the tubular esophagus above the lower esophageal sphincter. Metaplastic columnar mucosa of the incomplete intestinal type above the lower esophageal sphincter is a more restrictive definition of Barrett’s esophagus. Incomplete intestinal metaplasia of the columnar epithelium is also known as specialized or distinctive Barrett’s epithelium and is recognized by the presence of goblet cells without the presence of intestinal absorptive cells. This type of epithelium is a high-risk marker for the development of neoplastic changes and eventually infiltrating adenocarcinoma of the esophagus. The goblet cells contain alican blue positive acidic mucins. Alican blue positive mucin in non-goblet cells alone is not sufficient evidence for distinctive Barrett’s mucosa. The distinctive Barrett’s mucosa is almost always chronically inflamed and may be associated with architectural irregularities and fibrosis. There may be active inflammation and irregular patches of intervening squamous mucosal islands. The squamous mucosa may grow over the columnar epithelium (squamous pseudo-regression) and this pseudo-regression may mask the neoplastic changes of the underlying columnar mucosa at endoscopy. The inflamed mucosa may also show regenerative atypia characterized by slight to moderate nuclear enlargement, mild degree of stratification, relatively uniform vesicular nuclei and often prominent nucleoli. The presence of active inflammation should always raise the threshold for diagnosis of dysplasia in Barrett’s mucosa.

Regenerative atypia must be distinguished from true dysplasia. Low and high- grade dysplasias are characterized by cytologic and architectural changes similar to colonic tubular and tubulo-villous adenomas. Low-grade dysplasia is characterized by stratification limited to the basal aspect of the epithelium, and nuclei showing elongation, regimentation, enlargement and hyperchromasia. Mitoses and a degree of crowding are characteristic. Full thickness stratification, absence of goblet cells, marked nuclear enlargement, disorderliness in the nuclear arrangement, rounding up of nuclei, marked variation of nuclear size and shape, coarse chromatin, and prominent macro-nucleoli are all features of high grade dysplasia. Back-to-back arrangement of glands, occlusion of gland lumena, and cellular necrosis are features worrisome for adenocarcinoma arising in high grade dysplasia. Small irregular glands, especially at the base of the mucosa, crowding of irregular glands, single infiltrating cells, solid sheets of tumor cells, necrosis, and stromal desmoplastic alterations are features of adenocarcinoma. The risk for harboring adenocarcinoma when high-grade dysplasia is detected on biopsy is high in patients who are not under surveillance, and when biopsies originate from polypoid lesions or stricture-associated Barrett’s mucosa.