Resection of pancreatic cystic neoplasms in recurrent acute pancreatitis prevents recurrent pancreatitis but does not identify more malignancies.

BACKGROUND: Recurrent acute pancreatitis (RAP) may be a presenting feature of and an indication for resection of pancreatic cysts, including intra-ductal papillary mucinous neoplasm (IPMN). Few data are available regarding the prevalence of malignancy and post-operative RAP in this population. AIM: To study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy. METHODS: This retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016. The prevalence of preoperative high-risk cyst features, and of neoplasia was compared between patients with and without RAP. To identify the cause of pancreatitis, all the patients had a detailed history of alcohol, smoking, medications obtained, and had cross-sectional imaging (contrast-enhanced computed tomography/magnetic resonance imaging) and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis. The incidence of RAP post-resection was the primary outcome. RESULTS: IPMN accounted for 101 cases (58.7%) {[branch duct (BD) 59 (34.3%), main duct (MD) 42] (24.4%)}. Twenty-nine (16.9%) presented with RAP (mean 2.2 episodes): 15 had BD-IPMN, 8 MD-IPMN, 5 mucinous cystic neoplasm and 1 serous cystic neoplasm. Malignancy was similar among those with vs without RAP for all patients [6/29 (20.7%) vs 24/143 (16.8%)] and IPMN patients [6/23 (26.1%) vs 23/78 (29.5%)], although tended to be higher with RAP in BD-IPMN, [5/15 (33.3%) vs 3/44 (6.8%), P = 0.04]. At mean follow-up of 7.2 years, 1 (3.4%) RAP patient had post-resection RAP. The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02 (P < 0.0001). CONCLUSION: Malignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP. In addition, specific cyst charac-teristics were not clearly associated with RAP. The incidence of RAP was markedly decreased in almost all patients following cyst resection.

Histologic features of autoimmune hepatitis: a critical appraisal.

We speculate that the "typical" histologic features (lymphoplasmacytic interface hepatitis, emperipolesis, and hepatocyte rosettes) of autoimmune hepatitis (AIH) are related to severity of hepatitis rather than etiology. We critically appraised various histologic features of AIH and compared them with cases of chronic hepatitis with similar inflammatory grade and fibrosis stage. Fifty-one patients with clinically confirmed AIH were identified at our institution, of which 43 biopsies (from 42 patients) were taken before initiation of therapy and formed the study group. Hepatitis C biopsies with similar grade and stage served as controls. Kupffer cell hyaline globules (KcHGs; P = .03), prominence of plasma cells in portal tracts (P = .003), "plasma-lymphocytic" inflammation (defined as plasma cells > lymphocytes), or as clusters (defined as ≥5) within portal tracts (P = .002) or lobules (P = .001) were significantly associated with AIH. Rosettes and emperipolesis lacked significance when controlled for inflammatory grade (rosettes, P = 1; emperipolesis, P = .4), supporting our hypothesis. Based on our findings, we developed a modified scoring system in which typical features require the presence of both (1) prominent plasma cells (plasma cells comprise ≥20% of inflammatory cells or presence of plasma cell clusters) and (2) KcHG. "Compatible" features include prominent plasma cells but lack KcHG, and "atypical" features include the presence of another disease process. Although application of this scoring system in our patients decreased the sensitivity to 77% (from 100%), it increased the specificity to 67% (from 0%). Further studies with different control groups are needed to validate these findings.

Clear cell hepatocellular carcinoma diagnosed by bile duct brushing cytology.

Clear cell hepatocellular carcinoma (CCHCC) is an uncommon morphologic variant of HCC and rarely invades into the main bile ducts. Here we describe a case of CCHCC that was diagnosed by bile duct brushing cytology. Liquid-based preparation of brushing specimen showed clusters of atypical epithelial cells with abundant clear cytoplasm, round nuclei, and occasional intranuclear inclusions. The tumor cells were positive for HepPar-1 and arginase 1, suggestive of their hepatic origin. The overall morphologic and immunophenotypic features were consistent with CCHCC. The cytological diagnosis was confirmed by histopathologic examination of the resected tumor.

Colitis Following Initiation of Sofosbuvir and Simeprevir for Genotype 1 Hepatitis C.

Sofosbuvir and simeprevir are used for the treatment of chronic hepatitis C (HCV) genotype 1. Both drugs have been well-tolerated, with diarrhea noted in 6% cases with sofosbuvir, 16% with sofosbuvir plus simeprevir, and 0% with simeprevir. No prior reports exist of colitis secondary to either drug or their combination. We report a patient with no prior history of inflammatory bowel disease who developed significant bloody diarrhea within 2 weeks of sofosbuvir/simeprevir initiation. Colonoscopy and biopsy confirmed pancolitis, which responded to mesalamine and completion of sofosbuvir/simeprevir.

Appropriate use of special stains for identifying Helicobacter pylori: Recommendations from the Rodger C. Haggitt Gastrointestinal Pathology Society.

Helicobacter pylori is a major cause of gastroduodenal injury, gastric cancer, and lymphoma, and, thus, there is great interest in its detection and eradication. Several detection methods are available, including histochemical and immunohistochemical stains. Application of these stains in clinical practice is heterogenous, to say the least. Although they were developed to enhance H. pylori detection, changing practice models, financial considerations, and a perceived need for rapid case turnaround have led to their widespread use in routine staining studies ordered reflexively on all gastric biopsies. Emerging data suggest that most of these stains are not needed to establish a diagnosis of H. pylori infection, and their added value when biopsies show minimal, or no, inflammation is not clear. In this manuscript, the Rodger C. Haggitt Gastrointestinal Pathology Society puts forth recommendations regarding ancillary stain usage for H. pylori detection based upon critical literature review and collective experience. Pathologists rarely, if ever, detect H. pylori in "normal" biopsies, but readily observe them in optimally stained hematoxylin and eosin sections from infected patients. Therefore, we suggest that use of ancillary stains is appropriate when biopsies show chronic, or chronic active, gastritis without detectable H. pylori in hematoxylin and eosin-stained sections, but performing them "up front" on all gastric biopsies is generally unnecessary. Application of these stains to nongastric biopsies and polyps is appropriate in an extremely limited set of circumstances. It is our hope that recommendations provided herein will provide helpful information to gastroenterologists, pathologists, and others involved in the evaluation of patients for possible H. pylori infection.

Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport.

The Brunner's glands of the proximal duodenum exert barrier functions through secretion of glycoproteins and antimicrobial peptides. However, ion transporter localization, function, and regulation in the glands are less clear. Mapping the subcellular distribution of transporters is an important step toward elucidating trafficking mechanisms of fluid transport in the gland. The present study examined 1) changes in the distribution of intestinal anion transporters and the aquaporin 5 (AQP5) water channel in rat Brunner's glands following second messenger activation and 2) anion transporter distribution in Brunner's glands from healthy and disease-affected human tissues. Cystic fibrosis transmembrane conductance regulator (CFTR), AQP5, sodium-potassium-coupled chloride cotransporter 1 (NKCC1), sodium-bicarbonate cotransporter (NBCe1), and the proton pump vacuolar ATPase (V-ATPase) were localized to distinct membrane domains and in endosomes at steady state. Carbachol and cAMP redistributed CFTR to the apical membrane. cAMP-dependent recruitment of CFTR to the apical membrane was accompanied by recruitment of AQP5 that was reversed by a PKA inhibitor. cAMP also induced apical trafficking of V-ATPase and redistribution of NKCC1 and NBCe1 to the basolateral membranes. The steady-state distribution of AQP5, CFTR, NBCe1, NKCC1, and V-ATPase in human Brunner's glands from healthy controls, cystic fibrosis, and celiac disease resembled that of rat; however, the distribution profiles were markedly attenuated in the disease-affected duodenum. These data support functional transport of chloride, bicarbonate, water, and protons by second messenger-regulated traffic in mammalian Brunner's glands under physiological and pathophysiological conditions.

Ipilimumab-induced perforating colitis.

Recently, a monoclonal antibody to cytotoxic T-lymphocyte-associated antigen 4, ipilimumab, was approved for the treatment of metastatic melanoma. One of the most common side effects associated with this therapy is diarrhea and colitis. We report 3 cases of perforating colitis induced by ipilimumab requiring colectomy. The histologic findings of mucosal biopsies have been previously described. Herein, we describe novel associated histologic findings (pseudopolyp formation, fissuring ulcers, dilated crypts, and lack of intraepithelial lymphocytosis and epithelial apoptosis) of segmental resections in patients who required subtotal colectomy after perforation due to the severity of their ipilimumab-induced colitis. Although steroid therapy is the standard treatment for ipilimumab-induced colitis, surgery may be necessary. In the setting of progressive or worsening diarrhea after steroid therapy in patients with colitis, bowel perforation should be considered.

Hepatocellular carcinoma: histologic considerations: pure, mixed, and motley.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor seen in adults. The histopathologic diagnosis of classic or conventional differentiated HCC is seldom challenging, however, HCC is a particularly heterogeneous tumor. HCC often has a medley of morphologic features that are either challenging to recognize as hepatocellular, or represents components that are of complex histogenesis. This review focuses on the heterogeneous nature of HCC, with discussion of the histologic variants, some of which the clinical significance is unknown. In some cases, a lack of numbers precludes elucidating the clinical significance of these variants. Ultimately, larger studies are needed to determine the diagnostic and prognostic relevance of the phantasmagoria within HCC.

Pathology of the liver in copper overload.

Copper accumulation in the liver is associated with cellular and apoptotic injury. Wilson disease is the most well-characterized disorder of disordered copper metabolism. Other less-common disorders include Indian childhood cirrhosis, endemic Tyrolean infantile cirrhosis, and idiopathic copper toxicosis. The histopathologic spectrum of the liver in Wilson disease is extremely variable and overlaps among the different entities, though this review will focus on the pathology of Wilson disease. The findings lack specificity, although characteristic findings are observed. Unlike other disorders of copper overload, the pathologic changes are typically sequential, ranging from little or no significant findings to cirrhosis with or without widespread hepatocellular damage. Steatosis and glycogenated nuclei are frequent. Staining of copper is an unreliable method of diagnosis of Wilson disease, whether there are minimal histologic abnormalities or chronic liver disease. Copper and copper-associated protein accumulation may also be seen in chronic biliary obstructive processes.

Cancer and Leukemia Group B Pathology Committee guidelines for tissue microarray construction representing multicenter prospective clinical trial tissues.

Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups. A principal goal is to maximize the number of assays with this precious tissue. However, production strategies for these arrays have not been standardized, possibly decreasing the value of the study. In this article, members of the Cancer and Leukemia Group B Pathology Committee relay our experiences as array facility directors and propose guidelines regarding the production of high-quality TMAs for cooperative group studies. We also discuss statistical issues arising from having a proportion of patients available for TMAs and the possibility that patients with TMAs fail to represent the greater study population.

Serous cystadenoma in communication with the pancreatic duct: an unusual radiologic and pathologic entity.

Cross-sectional imaging is frequently used in the diagnosis of pancreatic cysts, but there can be overlap in radiographic appearance. We present a case of a patient with presumed intraductal papillary mucinous neoplasm (IPMN) who was ultimately found to have a serous cystadenoma in communication with the pancreatic duct. A literature search for serous cystadenoma communicating with the pancreatic duct was performed and the data was reviewed in the context of this case report. Three reports of patients with serous cystadenoma communicating with the pancreatic duct were identified. Review of current data revealed that endoscopic ultrasound (EUS) has an important role in distinguishing between pancreatic cystic lesions preoperatively. Distinguishing between serous and mucinous cystadenomas and IPMN is essential to guide appropriate management. Although communication with the pancreatic duct is usually pathognomonic of IPMN, rarely this may be a misdiagnosis of a serous cystadenoma and EUS may be necessary for further evaluation. If EUS cannot be performed, resection is favored to avoid undertreating a premalignant lesion.

Differences in germinal centre and non-germinal center phenotype in gastric and intestinal diffuse large B-cell lymphomas.

The gastrointestinal tract is the most common extranodal site of lymphoma, and the most common gastrointestinal lymphoma is diffuse large B-cell type (DLBCL). DLBCL can be separated into germinal centre (GCP) and non-germinal centre phenotypes (non-GCP) using CD10, BCL-6 and MUM1 immunohistochemistry, but primary gastrointestinal DLBCL has not been extensively studied. We investigated 48 cases of primary gastrointestinal DLBCL (33% involving the small intestine, 50% the stomach, 13% the large intestine and 4% the ileocecal junction) and found that most (88%) DLBCL in the intestines were of GCP, while only 58% of gastric DLBCL were of GCP. This difference in GCP and non-GCP in gastric vs. intestinal DLBCL may be due to variations in lymphomagenesis reflecting acquired vs. native mucosa-associated lymphoid tissue. There was no significant difference in either overall survival or disease-free survival between the germinal centre and non-germinal centre groups. The distribution of Helicobacter pylori in different gastric DLBCL phenotypes raises interesting questions about the pathogenesis of H. pylori-associated lymphomas.

Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas.

Definitive diagnosis of malignant mesothelioma in small specimens can be extremely difficult based on morphology alone. Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as the most common genetic alteration in malignant mesotheliomas. Recent studies demonstrated that this alteration may be useful for differentiating benign from malignant mesothelial proliferations in cytology specimens. The aim of this study was to evaluate the diagnostic utility of homozygous deletion of 9p21 assessed by fluorescence in situ hybridization (FISH) in mesothelial proliferations involving serosal surfaces in paraffin-embedded tissue. p16 protein immunoexpression was also explored as a potential diagnostic aid. FISH analysis demonstrated homozygous deletion of the 9p21 locus in 35 of 52 cases (67%) of pleural mesothelioma and in 5 of 20 cases of peritoneal mesothelioma (25%) (P<0.005). None of 40 cases of reactive pleural mesothelial proliferations showed p16 deletion (P<0.005). Loss of immunoexpression of p16 was observed in 71% of the peritoneal mesotheliomas, 40% of the pleural malignant mesotheliomas and 15% of the reactive mesothelial cells. Homozygous deletion did not correlate with p16 protein expression in any of the studied groups. Our study suggests that 9p21 homozygous deletion assessed by FISH on paraffin-embedded tissue may be helpful for differentiating between malignant mesotheliomas and reactive mesothelial proliferations. A discrepancy between p16 protein expression and homozygous deletion suggests that other molecular mechanisms may play a role in p16 protein expression in mesothelial proliferations.