Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis (UC), atypical UC, Crohn’s disease (CD) and IBD unclassified. Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid (non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD, is histologically characterized by increased intraepithelial lymphocytes (> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis, villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.

Background:We present a rare case of neonatal cholestasis in a female infant with Gaucher Disease (GD), who received liver transplantation. We review the relevant literature on similar disease presentations. Methods:A chart review of the index case was performed. PubMed and Medline databases were searched to identify other cases. Results:A 4-day-old female was referred with conjugated hyperbilirubinemia.Physical examination revealed icterus with hepatosplenomegaly and normal neurologic examination. The diagnosis of GD was confirmed through liver biopsy, low glucocerebrosidase enzyme activity, and two pathogenic mutations in GBA gene.Despite early initiation of ERT, the patient had worsening of her liver failure and underwent a left lateral segment liver transplant from a living donor at 7 months of age. She experienced improvement of her liver enzymes and coagulation, but passed away at 8 months due to the late onset of neurologic involvement. Nine other cases of GD presenting with neonatal cholestasis have been reported. Forty-four percent (4/9) of cases received ERT and none were considered for transplant. Overall, the literature suggests a poor prognosis with death reported in 77% (7/9) cases.

Background and Aims: Wilson disease (WD) has diverse presentations that frequently mimic other liver diseases. Distinguishing WD from non-alcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH), can be difficult and has critical implications for medical management. This study aimed to examine the utility of histological features of WD in children compared to those with NAFLD and AIH. Methods: A review of liver biopsy slides was performed in children with a clinical and/ or genetic diagnosis of WD, seen at the Hospital for Sick Children between 1981 and 2019 and compared to controls with NAFLD and AIH. 37 children with WD and 37 disease controls (20 NAFLD; 17 AIH) were included. Three pathologists, blind to clinical details and diagnosis, reviewed all liver biopsies to reach consensus. Clinical and histopathologic features were compared between groups.Results: Most WD cases displayed steatosis or steatohepatitis on histology (34/37), active AIH-pattern in 1 and inactive cirrhosis in 2 cases. Electron microscopy (EM) findings of mitochondrial abnormalities including dilated tips of cristae, pleomorphism, membrane duplication and dense matrix were more frequent in the WD group as compared to disease controls (p < 0.0001). In WD, dilated tips of mitochondrial cristae had a sensitivity of 91% and specificity of 86%, best among EM features. Conclusions: Light microscopic findings display considerable overlap among children with WD, NAFLD and AIH. Ultrastructural findings of mitochondrial abnormalities are important to distinguish WD from NAFLD and AIH. EM examination should be considered essential in the diagnostic work-up of paediatric liver biopsies.

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Background Basal plasma cells (BPC) are a diagnostic criterion for inflammatory bowel disease (IBD) and their persistence following therapy also indicates an increased risk of relapse. However neither the definition of basal plasma cells nor what is normal has been well established. We examined these parameters and determined whether there is reginal variability throughout the large bowel. Methods We looked at two patient populations. Group A) Biopsies from 6 standardised sites around the colon (cecum to rectum) from 37 patients who had normal colonoscopy at IRCCS Sacro Cuore Hospital, Negrar, Verona, Italy for symptoms suggesting irritable bowel syndrome, who were free of all medical therapy. Group B) a validation cohort from Mt Sinai Hospital Toronto using sections from the same 6 sites from 16 subtotal and total colectomy specimens performed for non-obstructing colonic carcinoma, primarily Lynch syndrome. Basal plasma cells were counted between two crypts in both the basal 5%, and the basal 20% of the mucosa. A partitioned visual analogue scale (PVAS) was also developed to see if this could replace counting, especially as the distance between crypts in IBD is variable Results In group A, in the lowest 5% part of the lamina propria, basal plasma cells were found throughout the large bowel and were highest in the proximal colon and lowest in the rectosigmoid. The maximum number of plasma cells between crypts was seven for the cecum and two for the rectum, with a gentle gradation between these two. The PVAS (range 1–5) varied from a maximum of 2 proximally to 1 distally. When the basal 20% was counted, the scores ranged from 35 in the cecum to 12 in the rectum, again with a gradation between, but the PVAS increased from a maximum of 3 proximally to 2 in the rectum. In group B the results were virtually to Group A and the PVAS scores were also virtually identical, The main difference was that at least one plasma cell was seen in all sections, likely because tissue sections encompass a much larger area. These results were all statistically significant. Conclusion The normal large bowel has a gradation of plasma cells that is highest proximally and lowest distally, however assessed, and needs to be taken into account when assessing the presence of basal plasma cells as an indicator of increased likelihood of relapse of IBD. The PVAS developed can replace the chore of counting, and is likely more meaningful when architectural distortion is present.