Sessile Serrated Adenoma With Dysplasia of the Colon.

OBJECTIVES: Sessile serrated adenomas with dysplasia (SSADs) of the colon are transitional lesions between sessile serrated adenomas (SSAs) and a subset of colorectal adenocarcinomas. We wished to gain insight into the relative percentages and significance of SSAD subtypes. METHODS: Retrospective (2007-2012) clinicopathologic review of colorectal polyps initially regarded as having mixed serrated and dysplastic elements. SSADs were subdivided into those with cap-like adenomatous dysplasia (ad1), non-cap-like adenomatous dysplasia (ad2), serrated dysplasia (ser), minimal dysplasia (min), and dysplasia not otherwise specified (nos). MLH1 immunostaining was performed on many. RESULTS: SSADser (7.7%) had a greater propensity for right colon, women, and MLH1 loss vs the entire cohort. SSAad1 (11.6%) had the least female preponderance, was least likely to have MLH1 loss, and was most likely to affect the left colorectum. SSAD with MLH1 loss was associated with an increased burden of SSAs in the background colon (P = .0003) but not tubular adenomas or hyperplastic polyps. Most SSADs (ad2 and nos groups, 80% combined) showed difficult-to-classify dysplasia, intermediate MLH1 loss rates, and intermediate clinical features. CONCLUSIONS: While some trends exist, morphologically subclassifying SSADs is probably not justified in routine clinical practice. MLH1 loss portends a greater burden of SSAs in the background colon.

Diagnostic challenges of focal nodular hyperplasia: interobserver variability, accuracy, and the utility of glutamine synthetase immunohistochemistry.

AIMS: The diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH. METHODS AND RESULTS: The study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non-lesional liver specimens). Pathologists were reasonably accurate (83.1%) in the diagnosis of FNH with haematoxylin and eosin alone. Ductular reaction and nodularity had the highest sensitivity for a diagnosis of FNH (88.1% and 82.2%, respectively), whereas central scar was the most specific feature (90.6%). The presence of two or more of the classic histological features had 89.6% sensitivity and 86.2% specificity for a diagnosis of FNH. Diagnostic accuracy was significantly higher with the addition of a GS stain. A map-like GS staining pattern was highly specific (99.3%) for FNH. However, GS staining was interpreted as non-map-like in 14.4% of reviews of true FNH cases, and overall interobserver agreement for interpretation of the GS staining pattern was only moderate (kappa = 0.42). CONCLUSIONS: Pathologists are reasonably accurate in the diagnosis of FNH on virtual biopsies, and GS staining improves accuracy. However, a subset of FNH cases remain challenging. Steatosis and a pseudo-map-like GS staining pattern were associated with increased difficulty. Therefore, although a map-like GS staining pattern is useful for confirmation of a diagnosis, the lack of a map-like GS staining pattern on needle biopsy does not necessarily exclude a diagnosis of FNH.

Significance of serrated epithelial change in inflammatory bowel disease.

OBJECTIVES: The clinical significance of hyperplastic polyp-like histologic changes in random biopsy samples ('serrated epithelial change' or SEC) from patients with inflammatory bowel disease (IBD) remains uncertain, with some studies suggesting an increased risk of dysplasia and even carcinoma. Controlled studies are few. We studied the significance of SEC on the development of dysplasia in follow-up surveillance of IBD patients in our system. METHODS: We identified 94 IBD patients with SEC and 187 IBD patients without SEC identified in index biopsy samples, and retrospectively collated results of follow-up surveillance samples in each group, with the development of dysplasia and/or adenocarcinoma as study endpoints. RESULTS: IBD patients with SEC had a 12.8% likelihood of developing dysplasia of any type within IBD-affected areas vs a 4.3% likelihood in non-SEC patients (follow-up in the 1-4 year range for each group). This was significant in univariate analysis (p = 0.013) but not in multivariate analysis, likely due to increased frequency of follow-up sampling in the SEC patients. One cancer developed in each group (p = NS). CONCLUSION: Our data, in the context of other studies, neither prove nor conclusively exclude an increased risk of dysplasia in IBD patients with SEC. But cancer risk appears low and continued surveillance at usual intervals seems reasonable.

Kratom induced severe cholestatic liver injury histologically mimicking primary biliary cholangitis: A case report.

BACKGROUND: Kratom is a psychoactive substance that is isolated from the plant Mitragyna speciosa. The leaves can be chewed fresh or dried, smoked, or infused similar to herbal teas. The plant leaves have been used by natives of Southeast Asia for centuries. The substance has been used for its stimulant activity at low doses, and as an opium substitute at higher doses due to a morphine like effect. CASE SUMMARY: A 37-year-old female with a history of depression and obesity (body mass index: 32) presented to emergency room with a week-long history of nausea, decreased appetite, fatigue, and two days of jaundice. On admission bilirubin was markedly elevated. Her condition was thought to be due to consumption of Kratom 2 wk before onset of symptoms. Liver biopsy showed changes mimicking primary biliary cholangitis. Patient's symptoms and jaundice improved quickly. CONCLUSION: The use of Kratom has been on the rise in recent years across the United States and Europe. Several case reports have associated adverse health impact of Kratom-containing products including death due to its ability to alter levels of consciousness. Only a few case reports have highlighted the hepatotoxic effects of Kratom. Even fewer reports exist describing the detailed histopathological changes.

Standardising the interpretation of liver biopsies in non-alcoholic fatty liver disease clinical trials.

BACKGROUND: There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised. AIM: To develop a consensus-based framework for standardising histologic assessment of liver biopsies in clinical trials of NAFLD. METHODS: An expert panel of 14 liver pathologists and three hepatologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 130 items derived from literature review and expert opinion were rated by each panel member on a 1-9 scale. Disagreement was defined as ≥5 ratings in the lowest (1-3) and highest (7-9) categories. Items were classified as inappropriate (median 1-3.5 without disagreement), uncertain (median 3.5-6.5 or any median with disagreement) or appropriate (median 6.5-9 without disagreement). Survey results were discussed as a group before voting. RESULTS: Current measures of disease activity and fibrosis may not fully capture important features of non-alcoholic steatohepatitis (NASH). Alternative methods to evaluate ballooning degeneration are needed. Panellists were uncertain whether portal inflammation, degree of steatosis and Mallory-Denk bodies are important measures of disease activity. Furthermore, it was felt that current staging systems do not capture the full spectrum of fibrosis in NASH. A consensus definition and sub-stages for bridging fibrosis are needed. The severity of perisinusoidal fibrosis should be captured at all stages. Lastly, a method to evaluate features of fibrosis regression should be developed. CONCLUSION: The operating properties of the modifications proposed should be evaluated prospectively to determine reliability and responsiveness.

Postpolypectomy Bleeding Prevention and More Complete Precancerous Colon Polyp Removal With Endoscopic Mucosal Stripping (EMS).

Background and Aims: Postpolypectomy bleeding and incomplete polyp removal are important complication and quality concerns of colonoscopy for colon cancer prevention. We investigated if endoscopic mucosal stripping (EMS) as a technical modification of traditional cold snare polypectomy to avoid submucosal injury during removal of non-pedunculated colon polyps could prevent postpolypectomy bleeding and facilitate complete polyp removal. Methods: This is an Internal Review Board exemption-granted retrospective analysis of 5,142 colonoscopies with snare polypectomy performed by one of the authors (ZJC) at Minnesota Gastroenterology ambulatory endoscopy centers during a 12-year period divided into pre-EMS era (2005-2012, n = 2,973) and EMS era (2013-2016, n = 2169) with systemic adoption of EMS starting 2013. Change in postpolypectomy bleeding rate before and after EMS adoption and EMS polypectomy completeness were evaluated. Results: Zero postpolypectomy bleeding case was found during EMS era (rate 0%) compared with 10 bleeding cases during pre-EMS era (rate 0.336%). This difference was statistically significant (P = 0.0055) and remained so after excluding 2 bleeding cases of pedunculated polyps (P = 0.012). All bleeding cases involved hot snare polypectomy. Histological examination of the involved polyps showed substantial submucosal vascular damage in contrast to a remarkable paucity of submucosa in comparable advanced polyps removed using EMS. Both biopsy and follow-up colonoscopy examination of the polypectomy sites confirmed that EMS more completely removed non-pedunculated advanced polyps. Conclusions: EMS polypectomy was effective in preventing postpolypectomy bleeding and facilitated complete polyp removal.

Imaging Surveillance of Hypervascular Liver Lesions in Non-Cirrhotic Patients.

A consensus surveillance protocol is lacking for non-cirrhotic patients with hypervascular liver lesions presumed to represent hepatocellular adenomas. Patients with hypervascular liver lesions <5 cm not meeting criteria for focal nodular hyperplasia or hepatocellular carcinoma underwent surveillance with contrast-enhanced magnetic resonance imaging (MRI) 6, 12, and 24 months after baseline imaging. If lesions remained stable or decreased in size, then surveillance imaging was discontinued. Between 2011 and 2014, 116 patients with hypervascular liver lesions were evaluated. Seventy-nine patients were eligible for the surveillance protocol. Median follow-up was 24 months (range, 1-144 months). One patient (1 %) continued oral contraceptive pill (OCP) use and presented with hemorrhage requiring embolization 5 months after initial diagnosis. Ten patients (13 %) underwent elective embolization or surgical resection for size ≥5 cm. The remaining 68 patients (86 %) continued surveillance without hemorrhage or malignant transformation. Risk factors for requiring intervention during the surveillance period included younger age, larger lesion size, and estrogen use (all p < 0.05). Patients with hepatocellular adenomas <5 cm can safely be observed after discontinuing OCP with serial imaging 6, 12, and 24 months after diagnosis. If lesions remain stable or decrease in size, then longer-term surveillance is unlikely to identify patients at risk for complications.

The pathology of serrated colorectal neoplasia: practical answers for common questions.

In the past 10-15 years, recognition and considerable understanding of much of the so-called 'serrated pathway' of colorectal neoplasia has emerged, although much remains to be discovered. Key elements appear to be a propensity for the elderly, females more than males, and right colon; precursor lesions with serrations; and frequent BRAF mutations, hypermethylation (particularly involving the MHL1 promoter), and resultant dysfunctional DNA mismatch repair and microsatellite instability (MSI) of the colorectal adenocarcinomas. For the anatomic pathologist, this has created challenges in sometimes having to morphologically subdivide once-comfortable hyperplastic polyps into hyperplastic polyps and 'sessile serrated adenoma/polyps' (SSA/Ps), learn to distinguish these from 'traditional' serrated adenomas, and learn to recognize biologically progressing forms of SSA/Ps known as 'sessile serrated adenoma with cytological dysplasia'. The goal of this article is to highlight for the practicing anatomic pathologist the current status of our understanding of serrated colorectal neoplasms from a practical perspective.

Appendiceal or cecal endometriosis with intestinal metaplasia: a potential mimic of appendiceal mucinous neoplasms.

Appendiceal or cecal endometriosis uncommonly presents diagnostic challenges, but rare cases with intestinal metaplasia can mimic mucinous tumors of the appendix. We describe 6 cases of appendiceal or cecal endometriosis with intestinal metaplasia that grossly and microscopically mimicked appendiceal mucinous tumors. The cases were characterized by marked mural hypertrophy and elastosis, with distortion of the appendix, and virtual obliteration of the lumen of the appendix. All cases had conventional endometriosis, together with varying amounts of endometriosis with intestinal-type epithelium. In 2 cases, scant or virtually no stroma around some mucin-filled glands made their recognition as endometriosis more difficult. None of the cases had dysplasia of the mucinous epithelium. All patients had benign follow-up (mean 3.6 y). Endometriosis with intestinal metaplasia is a rare phenomenon that, when it occurs in the appendix or cecum, may lead to misdiagnosis as a low-grade appendiceal mucinous neoplasm or mucinous carcinoma.

Barrett's esophagus is frequently overdiagnosed in clinical practice: results of the Barrett's Esophagus Endoscopic Revision (BEER) study.

BACKGROUND: The published prevalence of Barrett's esophagus (BE) varies from 0.9% to 25%, in part because of differences in the endoscopic interpretation of the disease. OBJECTIVE: We studied the accuracy of diagnosis in 130 patients previously labeled as having BE. Our aim was to determine the interobserver consistency of endoscopic findings and assess the percentage of patients with confirmed BE versus those with a revised diagnosis. DESIGN/SETTING/PATIENTS: Patients previously diagnosed with BE of any length and due for surveillance endoscopy were eligible for study. INTERVENTIONS: After intensive consensus anatomic and endoscopic review, study patients underwent endoscopy and biopsy by 1 of 3 endoscopists. BE was defined as any length of columnar-lined esophagus with goblet cells. MAIN OUTCOME MEASUREMENTS: Patients were photographed/videotaped for review by the other 2 endoscopists, and BE was either confirmed or revised. RESULTS: Eighty-eight patients (67.7%) had confirmed BE, and 42 (32.3%) had their diagnosis revised to no BE (95% confidence interval, 24.4%-41.1%) because there was no visible columnar-lined esophagus proximal to the gastric folds or no goblet cells were found on biopsy. BE length, site of previous endoscopy, age, sex, and hiatal hernia size were predictors of revision. All 3 endoscopists agreed on all confirmed BE cases and 38 of 42 of those revised. LIMITATIONS: Retrospective analysis, possible sampling error. CONCLUSIONS: BE is overdiagnosed in clinical practice with important implications for patient care including increased costs, reduced insurability, and psychological stress. The true BE cancer risk may also be underestimated. This study suggests the need for a better definition of the gastroesophageal junction, stricter accountability for BE diagnosis, and improved endoscopic education.

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.

Rare presentation of a gastrointestinal stromal tumor with spontaneous esophageal perforation: A case report.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) of the alimentary canal are malignant tumors with <1% of cases diagnosed in esophagus. These cases require special consideration given their close proximity to vital structures and propensity to be highly aggressive. Management of patients with GISTs has been transformed since the introduction of tyrosine kinase inhibitors. In this report, we present an unusual case of GIST with spontaneous esophageal perforation. PRESENTATION OF CASE: A 39-year-old Caucasian male presented to our hospital with complaints of severe chest and abdominal pain. A diagnostic chest radiograph revealed a moderate right-sided pleural effusion. Subsequently, an esophagram demonstrated a perforation proximal to an elongated stricture in the distal esophagus. A left thoracotomy was performed whereby a large mediastinal mass firmly attached to the esophagus and gastroesophageal junction was encountered. The neoplasm involved proximal one-third of the stomach and perforated into the right hemithorax. Histopathological evaluation of the tumor led to a diagnosis of GIST. DISCUSSION: GISTs of the gastroesophageal junction are uncommon and may rarely present with esophageal perforation. The standard of care for treating GIST at present includes tyrosine kinase inhibitors. This pharmacologic agent, along with improved surgical techniques and understanding of molecular markers for accurate diagnosis, will assuredly continue to improve overall survival of patients with GISTs. CONCLUSION: When stricture or achalasia is detected on imaging, GIST should be considered in the differential diagnosis for individual patients. Additionally, chest and abdomen CT scans of may be performed to confirm presence of a tumor mass, thereby ruling out achalasia.

Serrated lesions of the colorectum: review and recommendations from an expert panel.

Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.

Serrated Colorectal Neoplasia.

Until very recently, there was general acceptance in the pathology community that all serrated lesions of the colon and rectum without overt cytologic dysplasia were hyperplastic polyps and had no malignant potential. Although there are still several unanswered questions in regard to the relationship between the various serrated lesions, there is a better understanding of the relationship of sessile serrated adenoma to carcinoma. This article discusses hyperplastic polyps, sessile serrated adenoma, traditional serrated adenoma, mixed polyps, and serrated lesions in such conditions as idiopathic inflammatory bowel disease and mechanical trauma. The major focus of the content is on diagnostic features of these lesions.

Selective internal radiation therapy-induced extrahepatic injury: an emerging cause of iatrogenic organ damage.

Selective internal radiation therapy (SIRT) using Yttrium microspheres is a novel therapeutic approach to the localized treatment of hepatic tumors. It provides a distinct advantage over conventional external beam radiation in that its targeted nature allows the directed delivery of high doses of radiation to tumors while sparing the surrounding uninvolved hepatic parenchyma. Numerous studies have evaluated the safety and efficacy of SIRT, and it has been used to treat both primary and metastatic hepatic malignancies. However, SIRT is not without risk of complications, and has been known to cause various toxicities due to extrahepatic SIRT microsphere deposition. Reports of such injury have been only sparsely described in the pathology literature to date, and surgical pathologists therefore remain largely unaware of this phenomenon, which can potentially lead to misdiagnosis. Herein, we review the histopathology and pathophysiology of extrahepatic SIRT microsphere migration as a cause of iatrogenic tissue injury, highlighted by 3 examples of gastritis and 1 case of cholecystitis.

Iron overload syndromes and the liver.

Iron can accumulate in the liver in a variety of conditions, including congenital, systemic iron-loading conditions (hereditary hemochromatosis), conditions associated with systemic macrophage iron accumulation (transfusions, hemolytic conditions, anemia of chronic disease, etc), in some hepatitidies (hepatitis C, alcoholic liver disease, porphyria cutanea tarda), and liver-specific iron accumulation of uncertain pathogenesis in cirrhosis. The anatomic pathologist will be faced with the task of determining whether iron accumulation in the liver is significant and, if so, the nature of the disease that lead to the accumulation (ie diagnosis). The tools available to the pathologist include (most importantly) histologic examination with iron stain, quantitative iron analysis, clinical history, laboratory iron tests (serum iron and iron-binding capacity, serum ferritin) and germline genetic analysis for mutations in genes known to be associated with hemochromatosis (HFE, ferroportin, hepcidin, hemojuvelin, transferrin receptor-2). This article provides an overview of the above.

Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept.

Serrated polyps of the large intestine, including traditional hyperplastic polyps, traditional serrated adenomas, and more recently described sessile serrated adenomas, have gained increased recognition in recent years because of growing evidence that one of these lesions, the sessile serrated adenoma, might be the precursor lesion for some cases of microsatellite unstable colorectal carcinoma. Nevertheless, there has been some reluctance to embrace the concept of sessile serrated adenoma, and numerous diagnostic challenges exist. This article, which grew out of the Roger C. Haggitt Gastrointestinal Pathology Society Forum presented in Vancouver, Canada, March 6, 2004 as part of the annual meeting of the United States-Canadian Academy of Pathology, reviews the morphologic and molecular evidence for the concept of various polyps in the general category of serrated polyps of the large intestine, in particular the lesion known as the sessile serrated adenoma, and provides a conceptual framework for diagnosis of these lesions.

Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis.

Fibrolamellar carcinoma arises in noncirrhotic livers of young individuals and has been considered to be less aggressive than conventional hepatocellular carcinoma. This study compares survival and clinicopathologic features of fibrolamellar carcinoma with hepatocellular carcinoma arising in noncirrhotic and cirrhotic livers. Clinical and pathologic features including age, gender, tumor size, stage and survival were recorded in 20 resected cases of fibrolamellar carcinoma. Survival was compared with resected hepatocellular carcinoma without (n=32) and with cirrhosis (n=30). Proliferative activity was determined by immunohistochemistry for Ki-67. In all, 12 (60%) patients with fibrolamellar carcinoma died during follow-up; the 5-year survival was 45%. Mortality in fibrolamellar carcinoma was higher with metastatic disease at presentation (6/7, 86% vs 5/13, 39%, P=0.06). Age, gender and tumor size did not correlate with survival. The 5-year (45 vs 56%, P=0.4) as well as overall survival (40 vs 56.3%, P=0.3) was similar in fibrolamellar carcinoma and hepatocellular carcinoma without cirrhosis. The 5-year and overall survival in hepatocellular carcinoma with cirrhosis was 27 and 23.3%, respectively, which was not significantly different compared to fibrolamellar carcinoma (P=0.2). Among the cases without metastases at presentation, 5-year survival in fibrolamellar carcinoma (62%) and hepatocellular carcinoma without cirrhosis (57%) was significantly better (P=0.03) than hepatocellular carcinoma with cirrhosis (27%). The mean Ki-67 index was similar in all three groups (P=0.1). In conclusion, fibrolamellar carcinoma is an aggressive neoplasm with 45% 5-year survival and overall mortality of 60%. Nearly half the patients develop lymph node or distant metastasis. The prognosis of fibrolamellar carcinoma is similar to conventional hepatocellular carcinoma. Among nonmetastatic cases, the prognosis is better in fibrolamellar carcinoma and hepatocellular carcinoma without cirrhosis compared to hepatocellular carcinoma with cirrhosis. The better outcome in fibrolamellar carcinoma appears to be due to the absence of cirrhosis rather than its distinct clinicopathologic features.