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Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome associated with mutation in the adenomatous polyposis coli (APC) gene, a tumour suppressor located on chromosome 5q21. Attenuated familial adenomatous polyposis (AFAP) is a variant associated with fewer and later onset of colon polyps. AFAP-associated APC mutations have largely been found before codon 157, in exon 9 or after codon 1595. We present the case of a 44-year-old man incidentally found to have numerous gastric polyps during bariatric surgery, with innumerable polyps in the remaining part of the stomach and the entire colon, with rectal sparing, consistent with AFAP phenotype. Genetic testing demonstrated the c.7682dup (p.Ser2562Lysfs*21) variant in exon 15 of APC. This represents a previously undescribed APC mutation. This mutation likely yields end-binding protein 1 and human disc large binding protein inactivation, causing cell cycle microtubule dysregulation and tumour suppressor inactivation. Through loss of these regulatory mechanisms, this mutation is associated with AFAP phenotype. The patient was treated surgically and is doing well.

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Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60-70 μm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserved the anatomy of this structure, demonstrating that it is part of the submucosa and a previously unappreciated fluid-filled interstitial space, draining to lymph nodes and supported by a complex network of thick collagen bundles. These bundles are intermittently lined on one side by fibroblast-like cells that stain with endothelial markers and vimentin, although there is a highly unusual and extensive unlined interface between the matrix proteins of the bundles and the surrounding fluid. We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia. These anatomic structures may be important in cancer metastasis, edema, fibrosis, and mechanical functioning of many or all tissues and organs. In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.

Background: Russell Body Gastritis (RBG) is considered to be a rare histologic finding that has an unclear pathogenesis and an unpredictable clinical outcome. We sought to clarify the frequency and significance of RBG by assessing their associated histology and relationship with the local microbiome. Design: We reviewed all 220 gastric biopsies over a 2-month period at 1 institution for the presence and density of Russell bodies (RB). In biopsies with RB, the quantity of RB was manually counted using light microscopy at 200x magnification in every biopsy level (3068 sections) and the sectional area was estimated using a 1x1 mm grid overlay. RB density was calculated by dividing the total quantity of RB in all sections by the total sectional area. 48 additional patients, which corresponded to an extra 100 histologic biopsies, were consented at the same visit for an extra gastric biopsy for 16S rRNA sequencing, and these microbiome profiles were correlated with the highest RB density per patient. Results: Russell bodies (RB) were frequent in gastric biopsies (43% of all gastritides) and the RB density significantly increased with more severe gastritides (p<0.001, n=320). The gastric microbiome globally differed in beta diversity between RB-positive and RB-negative cases by unweighted and weighted principal component analysis (p=0.03, p=0.007, n=48, respectively). In particular, Helicobacter and Streptococcus were significantly enriched in gastritis with RB and their abundances correlated with RB density (p=0.0002, r=0.51; p=0.009, r=0.37, n=48, respectively). Protonpump inhibitor (PPI) use reduced RB density per unit abundance of Streptococcus (p=0.0021, n=48). H. pylori abundance significantly correlated with RB density and two Streptococcus species (an unclassified Streptococcal species and S. anginosus) significantly correlated with RB density in H. pylori-negative gastritis (p=0.009, n=36, r=0.36; p=0.0025, n=36, r=0.51, respectively). 7 H. pylorinegative patients were followed for 1 year and variation in Streptococcus abundance reflected RB density (p=0.085, n=7). Conclusions: RB are common within the inflamed gastric mucosa and gastritis with RB is associated with Helicobacter and Streptococcus enrichment and consequent global shifts in the gastric microbiome. PPI dampens RB production, presumably through anti-inflammatory effects. Gastritis with RB might represent a reactive humoral response to bacteria within the gastric microbiome. Streptococcus species may influence chronic gastritis

Endoscopic mucosal biopsy may misplace mucosal elements into the submucosa of colonic adenomas, mimicking invasive adenocarcinoma. Biopsy-related misplacement can be more challenging to recognize than typical misplaced epithelium (pseudoinvasion) in pedunculated polyps. We compared the features of 16 polyps with biopsy-related misplaced epithelium with those of 10 adenomas with pseudoinvasion and 10 adenomas with invasive adenocarcinoma and performed Ki67 and p53 immunostaining on all cases. Features of misplaced epithelium in polyps referred to the Bowel Cancer Screening Program Expert Board in the United Kingdom were also evaluated for the same morphologic features. Biopsy-related epithelial misplacement occurred in adenomas throughout the colon and often appeared infiltrative (69%), including epithelial cells singly dispersed within reactive fibroinflammatory stroma or granulation tissue (44%). Misplaced epithelium displayed only low-grade cytologic features and was associated with extruded mucin (75%), tattoo pigment (63%), and misplaced normal glands (38%); scant lamina propria and muscularis mucosae were often present (88% and 44%, respectively). Cases referred to the Bowel Cancer Screening Program Expert Board also contained infiltrative-appearing misplaced epithelium (91%) that was cytologically low grade (72%), contained nondysplastic glands (11%), and showed other signs of injury. In contrast, misplaced epithelium in pedunculated polyps always had a lobular contour with a rim of lamina propria, hemorrhage, and/or hemosiderin. Invasive carcinomas showed malignant cytology and desmoplasia; most (70%) lacked features of trauma. Ki67 and p53 staining was patchy and weak in the misplaced epithelium, whereas invasive carcinomas showed increased staining for one or both markers. Pathologists should be aware that endoscopically manipulated adenomas may contain misplaced epithelium that simulates malignancy.

Sarcoidosis is a granulomatous disorder of unknown etiology involving multiple organ systems. Isolated neurosarcoidosis is exceedingly rare. This case report presents isolated trigeminal nerve sarcoidosis mimicking schwannoma in a patient presenting with symptoms of trigeminal neuralgia. Neuroimaging revealed a mass associated with trigeminal nerve which prospectively thought to represent schwannoma. However, surgical pathology was consistent with sarcoidosis. Given great overlap in imaging characteristic of tumors in the Meckel's cave intraoperative frozen section biopsy may be considered to rule out an inflammatory lesion.

Background and study aims: Surveillance intervals after colonoscopic resection of serrated polyps are partially predicated on the histology of the polyp(s) removed during the index exam. Histologic discrimination between sessile serrated adenomas/polyps (SSA/P) and hyperplastic polyps is challenging. We devised and tested a simple tool - an envelope - that gastroenterologists can integrate into routine colonoscopy practice to address this problem.Methods: In the "modified protocol," immediately after polypectomy each serrated polyp was flattened and enclosed in a paper envelope before being placed in formalin. In the pathology laboratory, each polyp was sectioned after processing. A two-site, prospective, randomized, single-blinded trial was performed to compare this modified protocol with the conventional protocol. Serrated polyps located proximal to the splenic flexure and 5 - 20 mm in diameter were included. A novel orientation score that measured the number of well-oriented crypts per unit area of polyp (higher orientation score = better orientation) was validated. Orientation score, SSA/P diagnosis rate, and inter-pathologist agreement were measured.Results: A total of 375 polyps were enrolled, of which 264 were identified for analysis. The mean orientation scores in the modified and conventional protocol groups were 3.11 and 1.13, respectively (P < 0.0001). SSA/Ps were diagnosed in 103/135 cases (76.3 %) in the modified protocol group vs. 54/129 (41.9 %) in the conventional protocol group (P < 0.0001). Inter-pathologist agreement was higher with the modified than the conventional protocol (77.0 % vs. 62.8 %; P = 0.015).Conclusion: Standard polyp handling techniques may be sub-optimal for interpretation of serrated polyps resected at colonoscopy, and may lead to inadvertent histologic "under-grading" of many lesions. Our intervention improved histopathologic interpretation and increased the SSA/P diagnosis rate.