Wide-area transepithelial sampling with 3-dimensional cytology: Does it detect more dysplasia or yield more hype?  Marcia Irene Canto, MD, MHS  Gastrointestinal Endoscopy  Volume 87, Issue 2, Pages 356-359 (February 2018) DOI: 10.1016/j.gie.2017.11.005 Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 1 Barrett’s esophagus, negative for dysplasia, standard preparation (H&E, orig. mag. ×20). This example displays prominent lamina propria with chronic inflammation and reactive changes. The nuclei at the base of the biopsy are larger and rounder than those toward the surface. There is reactive squamous epithelium at the upper left, the surface of which is lightly encrusted with acute inflammatory cells. The arrow indicates a deep gland/pit showing cytologic alterations that are readily recognized as reactive in the context of the architectural features of the sample. Gastrointestinal Endoscopy 2018 87, 356-359DOI: (10.1016/j.gie.2017.11.005) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 2 Barrett esophagus, negative for dysplasia, standard preparation, higher magnification of the indicated gland seen in Figure 1 (H&E, orig. mag. ×100). At very high magnification, the nuclei of the indicated gland appear enlarged and hyperchromatic (thin arrow), and an apoptotic body is indicated by the thick arrow. This gland is clearly not dysplastic in the context of the architecture of the sample, but were it viewed as a “naked” gland, it could easily be interpreted as dysplastic. Gastrointestinal Endoscopy 2018 87, 356-359DOI: (10.1016/j.gie.2017.11.005) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions

Figure 3 Barrett esophagus, negative for dysplasia, TP53 immunolabeling (orig. mag. ×20). This image shows a wild-type TP53 immunolabeling pattern. The basal layer of the squamous epithelium shows light nuclear labeling, which is to be expected because this tumor suppressor protein is active in the proliferative compartment of the epithelium. Similar light immunolabeling is also seen in the deeper nonneoplastic glands, as would be expected. Zones of striking nuclear labeling of the type described in basal pattern dysplasia are absent, and the light labeling disappears at the surface. In lesions with TP53 gene alterations, the abnormal TP53 protein has a long half-life and thus accumulates in the nuclei, resulting in dense strong nuclear TP53 labeling, absent in this sample. Alternatively, biallelic inactivation of the TP53 gene can also result in complete absence of protein expression in dysplastic nuclei, termed the “null pattern,” in contrast to the wild-type pattern seen here with weak labeling in cells in which tumor suppressor activity is at work. Gastrointestinal Endoscopy 2018 87, 356-359DOI: (10.1016/j.gie.2017.11.005) Copyright © 2018 American Society for Gastrointestinal Endoscopy Terms and Conditions