Lymphocytic esophagitis (LE) is an uncommon poorly defined histologic pattern. Its significance is largely unknown. The goal of our study was to characterize LE clinically, histologically, and immunophenotypically. Biopsies of 45 patients with LE and no intraepithelial granulocytes were selected throughout a 36-month period during routine diagnostic work. After reevaluation, complete absence of intraepithelial granulocytes was confirmed in 21 patients (LE-NG group), and few granulocytes were found in 24 patients (LE-FG). The control group consisted of 28 patients with active esophagitis consistent with reflux and overtly increased intraepithelial lymphocytes (REIL). The ratio of CD4:CD8 intraepithelial lymphocytes (IEL)>1 indicated predominance of CD4 IEL; the ratio ≤1 indicated predominance of CD8 IEL. Dysphagia was the primary complaint in 71%, 54%, and 39% of the patients with LE-NG, LE-FG, and REIL, respectively (P=0.04, LE-NG vs. REIL). Importantly, primary esophageal motility abnormalities were found in 10/11 (91%) tested LE-NG patients, 6/10 (60%) LE-FG patients, and 6/11 (54%) REIL patients. CD4 IELs were predominant in 81%, 50%, and 39% of LE-NG, LE-FG, and REIL cases, respectively (P=0.004, LE-NG vs. REIL), and in 90%, 83%, and 88% of the cases with primary motility abnormalities from the same groups. The prevalence of primary motility abnormalities was significantly higher in patients with CD4-predominant esophagitis than in patients with CD8-predominant esophagitis from all groups (21/24 [83%] vs. 2/8 [25%], P=0.005). A distinctive type of LE with predominance of CD4 IEL is associated with primary motility abnormalities suggesting a diagnostic utility of evaluating CD4 and CD8 subpopulations of T cells in LE.

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients.

Are deep neural networks trained on data from a single institution for classification of colorectal polyps on digitized histopathology slides generalizable across multiple external institutions? Findings: A new deep neural network was developed based on 326 slide images from our institution to classify the four most common polyp types on digitized histopathology slides. In addition to evaluation on an internal test set of 157 slide images, we evaluated the model on an external test set of 238 slide images from 24 institutions across 13 states in the United States.This model achieved mean accuracies of 93.5% and 87.0% on the internal and external test sets, respectively, which were comparable with the performance of local pathologists on these test sets.Meaning: Deep neural networks could provide a generalizable approach for the classification of colorectal polyps on digitized histopathology slides and if confirmed in clinical trials, could potentially improve the efficiency, reproducibility, and accuracy of one of the most common cancer screening procedures.

The diagnosis of gastric epithelial dysplasia, a precursor lesion of gastric adenocarcinoma, is hindered by interobserver variability and by its resemblance to regenerative changes. Loss of cell polarity, a histological feature of gastric epithelial dysplasia, may be difficult to ascertain, especially in the setting of inflammation or injury. A biomarker of cell polarity could be useful in diagnosis of dysplasia, but has not been reported. The Lethal giant larvae (lgl) gene controls apical-basal polarity of epithelial cells in Drosophila, and has properties of a tumor-suppressor gene. Two homologs, lgl1 and lgl2, are present in mammals and lgl2 mRNA is highly expressed in the stomach. The goal of our study was to test the hypothesis that Lgl2 protein expression and/or localization are disrupted in gastric epithelial dysplasia and adenocarcinoma. Routinely processed pathology specimens including 94 benign mucosae of digestive organs, in addition to 36 reactive gastropathy, 57 gastric epithelial dysplasia, and 77 gastric adenocarcinomas, were immunostained for Lgl2 protein. All normal, reactive, and chronically inflamed gastric epithelia showed basolateral Lgl2 staining. Normal esophageal, duodenal, colonic, biliary, and pancreatic duct mucosae, as well as gastric intestinal metaplasia, did not express Lgl2. All but one case each of gastric epithelial dysplasia and adenocarcinoma showed either complete loss of anti-Lgl2 immunoreactivity or diffuse, mostly weak, cytoplasmic staining. Complete loss of immunoreactivity was significantly more often observed in diffuse-type than in intestinal-type adenocarcinomas (79 vs 48%, respectively). Our data suggest that Lgl2 expression is either aberrantly localized or lost in gastric epithelial dysplasia and adenocarcinoma, whereas it is maintained in reactive gastric mucosa. We propose that Lgl2 may be a potential marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic specimens. However, the consistently negative anti-Lgl2 immunoreactivity seen in intestinal metaplasia does not allow differentiation of dysplasia from intestinal metaplasia with reactive change.

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Because HP versus SSP is not very reproducible the predictors of SSA/P that we identified, including size, location, and synchronous lesions, can offer some additional help to endoscopists when determining surveillance intervals in patients with serrated polyps. In addition, observed association between SSA/P with advanced conventional neoplasia (but not low-grade adenomas) suggests 2 distinct groups of patient predisposition, one with both advanced conventional and important serrated precursors (SSA/P) and the other largely restricted to nonadvanced conventional adenomas and HPs only. Whether the association reported here has to do with SSA/P diagnosis per se or generally larger size of SSA/P remains to be determined in future studies.

Extracellular Wnt ligands and their receptors of the Frizzled family control cell fate, proliferation, and polarity during metazoan development. Frizzled signaling modulates target gene expression through a beta-catenin-dependent pathway, functions to establish planar cell polarity in Drosophila epithelia, and activates convergent extension movements and intracellular Ca(2+) signaling in frog and fish embryos. Here, we report that a Frizzled receptor, Xenopus Frizzled 8 (Xfz8), activates c-Jun N-terminal kinases (JNK) and triggers rapid apoptotic cell death in gastrulating Xenopus embryos. This activity of Xfz8 required the cytoplasmic tail of the receptor and was blocked by a dominant inhibitor of JNK. Moreover, the cytoplasmic tail of Xfz8 targeted to the membrane was sufficient for activation of JNK and apoptosis. The apoptotic signaling was shared by a specific subset of Frizzled receptors, was inhibited by Wnt5a, and occurred in a Dishevelled- and T cell factor (TCF)-independent manner. Thus, our experiments identify a novel Frizzled-dependent signaling pathway, which involves JNK and differs from the beta-catenin-dependent and convergent extension pathways.