Are ulcers a marker for invasive carcinoma in barrett's esophagus? data from a diagnostic variability study with clinical follow-up

We correlated follow-up information from 138 patients with Barrett's esophagus and varying degrees of dysplasia with the presence of ulcers. Methods A group of pathologist participants were asked to contribute patients’ initial biopsy slides showing Barrett's esophagus (BE) without dysplasia and with epithelial changes indefinite for dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma. From the initial 250 cases used for a diagnostic reproducibility study, follow-up information was available for 138 patients. Results There were 44 cases submitted as BE, 22 as BE with epithelial changes indefinite for dysplasia, 26 as BE with LGD, 33 as BE with HGD, and 13 as BE with adenocarcinoma. Ulcers were present in 35/138 cases (25%), including 3/44 cases of BE without dysplasia (7%), 2/22 cases of BE with epithelial changes indefinite for dysplasia (9%), 0/26 cases of BE with LGD (0%), 10/33 cases of BE with HGD (30%), and 7/13 cases of BE with adenocarcinoma (54%). On follow-up, there were no invasive carcinomas detected among the BE without dysplasia group (median follow-up = 38.5 months). Adenocarcinomas were detected in 4/22 cases (18%) submitted as BE with epithelial changes indefinite for dysplasia at 19, 55, 60, and 62 months and in 4/26 cases (15%) of BE with LGD at 9, 9, 11, and 60 months. None of these carcinomas occurred in cases in which an ulcer was present in the initial biopsy specimen. Among the 33 HGD cases, 20 (60%) were found to have adenocarcinoma on subsequent resection specimens. The presence of an ulcer with HGD increased the likelihood of finding carcinoma in the resection specimen, as 8/10 biopsies (80%) of HGD patients with ulcers had carcinoma, compared to 12/23 biopsies (52%) of HGD patients without ulcers. All of the cases interpreted as adenocarcinomas on biopsy were found either to have invasive carcinoma on esophageal resection or to have metastases that were demonstrated in unresectable patients. Conclusion If an ulcer accompanies HGD in a biopsy specimen from a patient with BE, it is likely that invasive carcinoma is also present at that time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75186/1/j.1572-0241.2002.05420.x.pd

Pronounced squamous cell contamination in biliary tract cytology: A diagnostic pitfall

Squamous cells are rarely found in biliary tract cytology specimens, and when present are typically scant in quantity. Over an 8-year time period, two cases at our institution reporting abundant squamous cells were identified. Both patients underwent endoscopic retrograde cholangiopancreatography with bile duct brushings and removal of a migrated biliary stent. The migrated stents were retrieved using rat toothed forceps and required removal of the endoscope through the esophagus with the stent exposed to esophageal and oral mucosa outside of the endoscope. Cytologic examination of the accompanying biliary stent material accordingly revealed abundant benign squamous cells. However, bile duct brushings showed benign ductal epithelial cells without squamous cells. Prior and subsequent cytology and bile duct surgical pathology specimens did not show squamous metaplasia. Migrated biliary stents that require endoscopic withdrawal increase the risk of contaminating samples with squamous cells. Recognition of this unique scenario is important, as the differential diagnosis includes squamous metaplasia and squamous neoplasia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174946/1/dc25008_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174946/2/dc25008.pd

Adenomatoid tumours of the gastrointestinal tract – a case‐series and review of the literature

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171175/1/his14553_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171175/2/his14553.pd

Post-transplant lymphoproliferative disorder with ileal stricture masquerading as Crohn disease

Post-transplant lymphoproliferative disorders (PTLDs) are a group of hematopoietic proliferations classified into four categories depending on their morphology and resemblance to established lymphomas, including non-destructive, polymorphic (P-PTLD), monomorphic (M-PTLD) and classic Hodgkin lymphoma. They are a consequence of immunosuppression following solid organ or stem cell transplants and can occur at nearly any site with highly variable presentations. The two most important risk factors for the development of PTLD are immunosuppressive duration and intensity, rather than specific therapeutic agents, and pre-transplant EBV-seronegativity. We report a case of diffuse large B-cell lymphoma (DLBCL) M-PTLD with focal EBV-positivity diagnosed following small bowel resection in a 57-year-old woman status post remote bilateral lung transplant for cystic fibrosis and with long-term chronic idiopathic inflammatory bowel disease (CI-IBD), who was clinically thought to have Crohn disease (CD) following development of inflammatory ileal strictures. She underwent resection due to imminent small bowel obstruction, at which time the PTLD was discovered. No features of CD were identified, and the patient was successfully treated conservatively. Our case of M-PTLD DLBCL with focal EBV-positivity in a patient with a longstanding history of both bilateral lung transplant and CI-IBD demonstrates a unique presentation that was clinically thought to be CD in an EBV-seronegative patient. We aim to highlight the importance of considering PTLD when a transplant recipient develops a new lesion or mass, particularly as the risk of developing PTLD increases with duration of time following the transplant

Platform-independent gene expression signature differentiates sessile serrated adenomas/polyps and hyperplastic polyps of the colon

Abstract Background Sessile serrated adenomas/polyps are distinguished from hyperplastic colonic polyps subjectively by their endoscopic appearance and histological morphology. However, hyperplastic and sessile serrated polyps can have overlapping morphological features resulting in sessile serrated polyps diagnosed as hyperplastic. While sessile serrated polyps can progress into colon cancer, hyperplastic polyps have virtually no risk for colon cancer. Objective measures, differentiating these types of polyps would improve cancer prevention and treatment outcome. Methods RNA-seq training data set and Affimetrix, Illumina testing data sets were obtained from Gene Expression Omnibus (GEO). RNA-seq single-end reads were filtered with FastX toolkit. Read mapping to the human genome, gene abundance estimation, and differential expression analysis were performed with Tophat-Cufflinks pipeline. Background correction, normalization, and probe summarization steps for Affimetrix arrays were performed using the robust multi-array method (RMA). For Illumina arrays, log2-scale expression data was obtained from GEO. Pathway analysis was implemented using Bioconductor package GSAR. To build a platform-independent molecular classifier that accurately differentiates sessile serrated and hyperplastic polyps we developed a new feature selection step. We also developed a simple procedure to classify new samples as either sessile serrated or hyperplastic with a class probability assigned to the decision, estimated using Cantelli’s inequality. Results The classifier trained on RNA-seq data and tested on two independent microarray data sets resulted in zero and three errors. The classifier was further tested using quantitative real-time PCR expression levels of 45 blinded independent formalin-fixed paraffin-embedded specimens and was highly accurate. Pathway analyses have shown that sessile serrated polyps are distinguished from hyperplastic polyps and normal controls by: up-regulation of pathways implicated in proliferation, inflammation, cell-cell adhesion and down-regulation of serine threonine kinase signaling pathway; differential co-expression of pathways regulating cell division, protein trafficking and kinase activities. Conclusions Most of the differentially expressed pathways are known as hallmarks of cancer and likely to explain why sessile serrated polyps are more prone to neoplastic transformation than hyperplastic. The new molecular classifier includes 13 genes and may facilitate objective differentiation between two polyps