Susan Kornacki

Dysplasia and Dysregulation of Proliferation in Foveolar and Surface Epithelia of Fundic Gland Polyps From Patients With Familial Adenomatous Polyposis

Fundic gland polyps (FGPs) of the stomach are regarded as hamartomatous or hyperplastic/functional polyps that occur sporadically but at increased frequency in patients with familial adenomatous polyposis syndrome (FAP). There is controversy about the histopathology of FGPs, including occurrence of dysplasia. We, therefore, studied dysplasia in 270 sporadic FGPs from 216 patients and 49 FGPs from 24 patients with FAP. We evaluated dysregulation of epithelial proliferation manifested by loss of the normal inverse topographic distribution of Ki-67 proliferation marker and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) using immunohistochemistry in 27 sporadic FGPs and in 22 FGPs from patients with FAP. Dysplasia in foveolar and surface epithelia occurred in 12 of 49 (25%) FGPs in patients with FAP but in only 3 of 270 (1%) of sporadic FGPs (p < 0.000001). Fourteen of 49 (29%) of FGPs from patients with FAP were indefinite for dysplasia, as contrasted with 8 of 270 (3%) sporadic FGPs (p < 0.00001). The normal inverse topographic distribution of Ki-67 and p21(WAF1/CIP1) was maintained in 20 of 22 (91%) of FGPs negative for dysplasia but was lost in all (8 of 8) FGPs with dysplasia and in 11 of 19 (58%) FGPs that were indefinite for dysplasia (p = 0.00001). The results indicate that dysplasia can occur in foveolar and surface epithelia of FGPs, especially in patients with FAP, and often is preceded by dysregulation of epithelial proliferation when the morphologic abnormalities are indefinite for dysplasia.

Is gastroduodenal biopsy safe in patients receiving aspirin and clopidogrel?: a prospective, randomized study involving 630 biopsies.

Goals To assess prospectively the bleeding risk attributable to gastroduodenal biopsy in subjects taking antiplatelet medications. Background No prospective data exist regarding the bleeding risk attributable to endoscopic biopsy in patients taking antiplatelet agents. A majority of Western endoscopists withdraw antiplatelet agents before upper endoscopy, despite expert guidelines to the contrary. Study We performed a prospective, single-blind, randomized study in healthy volunteers participating in a larger study regarding the effect of antiplatelet agents on gastroduodenal mucosal healing. Multiple gastroduodenal biopsies were performed during 2 esophagogastroduodenoscopy in subjects dosed with aspirin enteric-coated 81 mg once daily or clopidogrel 75 mg once daily. Data for endoscopic bleeding, clinical bleeding, blood vessel size, and depth of biopsy in histology specimens were collected. Results Four hundred and five antral biopsies and 225 duodenal biopsies were performed during 90 esophagogastroduodenoscopy in 45 subjects receiving aspirin or clopidogrel. Median maximum blood vessel diameter per biopsy was 31.9 &mgr; (range: 9.2 to 133.8). About 50.8% of biopsy specimens breached the muscularis mucosa. In the clopidogrel group, no bleeding events were noted after 350 biopsies [upper confidence limit (UCL) for probability of bleeding=0.0085]. In the aspirin group, there were no clinical events (UCL=0.0106) and one minor endoscopic bleeding event (UCL=0.0169). Conclusions Consistent with expert guidelines, the absolute risk attributable to gastroduodenal biopsy in adults taking antiplatelet agents seems to be low. Half of routine biopsies enter submucosa. The largest blood vessels avulsed during biopsy correspond to midsized and large arterioles and venules.

The detection of premalignant colon polyps during colonoscopy is stable throughout the workday

BACKGROUND Recent studies have shown that colonoscopic polyp detection decreases as the workday progresses. This may reflect time-dependent factors such as colonoscopist fatigue and decreased colon cleanliness, which can be addressed through adaptations in colonoscopy practice. OBJECTIVE To test for time-of-day differences in adenomatous polyp (AP) and sessile serrated polyp (SSP) detection in a practice that uses split-dose bowel preparation and moderated daily colonoscopist procedure loads. DESIGN Retrospective chart review. SETTING Community-based, group gastroenterology practice. PATIENTS This study involved 2439 patients undergoing surveillance or screening colonoscopy. INTERVENTION Colonoscopy. MAIN OUTCOME MEASUREMENTS Detection rate of all premalignant polyps (PMPs), and of APs and SSPs, individually. RESULTS A total of 1183 PMPs were identified in 1486 eligible patients (mean PMP/colonoscopy = 0.80; PMP detection rate = 47%). In univariate and multivariate analyses, PMP detection as well as detection of APs or SSPs individually did not vary significantly in relation to the hour of the day. In a binary comparison of morning (am) versus afternoon (pm) procedures, the total polyp detection rate was 67% and 66%, respectively. For PMPs, APs, SSPs, and hyperplastic polyps (HPs), the am and pm detection rates were 46% and 47%, 41% and 44%, 8% and 8%, and 27% and 24%, respectively. Bowel preparation quality was independent of time of day and was rated excellent or good in 86% to 87% of cases. LIMITATIONS Retrospective, nonrandomized study. CONCLUSION Stable PMP, AP, SSP, and HP detection rates throughout the workday occur under certain practice conditions, including the use of split-dose bowel preparation and/or moderated daily colonoscopist procedure loads.

Diagnostic Challenges Caused by Endoscopic Biopsy of Colonic Polyps: A Systematic Evaluation of Epithelial Misplacement With Review of Problematic Polyps From the Bowel Cancer Screening Program, United Kingdom.

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.

Author Correction: Structure and Distribution of an Unrecognized Interstitium in Human Tissues

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Rare isolated trigeminal nerve sarcoidosis mimicking schwannoma

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 Meckels cave intraoperative frozen section biopsy may be considered to rule out an inflammatory lesion.