Gastric Plexiform Fibromyxoma: A Great Mimic of Gastrointestinal Stromal Tumor (GIST) and Diagnostic Pitfalls.

Through a multicenter study, we collected seven cases of gastric plexiform fibromyxoma including four females and three males, 21 to 79 y old (46.1 ± 10.1). All cases showed a unilocular lesion measuring 0.3 to 17 cm (5.3 ± 2.4), arising from antrum (5/7) or body (2/7). Six of the seven cases had intraoperative frozen sections and/or endoscopic ultrasound fine needle aspiration (EUS-FNA), and all of them were preoperatively or intraoperatively diagnosed as gastrointestinal stromal tumor (GIST). EUS-FNA material showed markedly elongated spindle cells with streaming oval to elongated nuclei with rounded ends. Histologically, the tumors exhibited a plexiform growth pattern and were composed of a rich myxoid stroma and cytologically bland uniform spindle cells without mitotic figures, with the exception of one case which displayed nuclear pleomorphism and increased mitosis. Immunostains showed the tumor cells to be focally positive for SMA (6/6), focally and weakly positive for desmin (3/6) and caldesmon (2/3), negative for CD117 (0/7), CD34 (0/7), DOG1 (0/4), and S100 (0/5). No mutations were identified on Next-Generation Sequencing test, and no loss of SDHB immunoreactivity was identified in the tumor with nuclear pleomorphism. One case was treated with Gleevec because of the initial diagnosis of GIST. All patients had a follow-up for up to 11 y, with no tumor recurrence or metastasis reported. Our results suggest that gastric plexiform fibromyxoma is rare and may be underrecognized and misinterpreted as GIST during intraoperative frozen section or preoperative EUS-FNA diagnosis without immunostains leading to inappropriate treatment.

Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp.

Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer-related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73% and a specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer-related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer.

Unusual Presentation of Cow's Milk Protein Allergy.

Cow's milk protein allergy (CMPA) is an abnormal immunologic response to bovine protein that can result in various gastrointestinal and cutaneous manifestations including diarrhea, failure to thrive, malabsorption, and even protein-losing enteropathy. We describe a case of a 7-month-old breastfed male who presented with severe atopic dermatitis, emesis, oily diarrhea, failure to thrive, electrolyte disturbance, and hemodynamic instability. Following stabilization, additional evaluation revealed concern for abetalipoproteinemia. Ultimately, the patient's symptoms resolved with introduction of an elemental formula and returned with reinitiation of cow's milk protein, confirming the diagnosis of severe CMPA. It is important for the general practitioner to be aware of the various presentations and have a high index of suspicion for CMPA as no symptom or diagnostic test is pathognomonic for diagnosis. Even though it can mimic other causes of malabsorption, a trial with extensively hydrolyzed or elemental formula should be attempted before undertaking invasive testing.

A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo.

Alpha 1-antitrypsin deficiency (AATD) is the most common genetic cause of liver disease in children and is associated with early-onset chronic liver disease in adults. AATD associated liver injury is caused by hepatotoxic retention of polymerized mutant alpha 1-antitrypsin molecules within the endoplasmic reticulum. Currently, there is no curative therapy for AATD. In this study, we selected small molecules with the potential to bind mutant alpha 1-antitrypsin (Z-variant) to inhibit its accumulation in hepatocytes. We used molecular docking to select candidate compounds that were validated in cell and animal models of disease. A crystal structure of polymerized alpha 1-antitrypsin molecule was used as the basis for docking 139,735 compounds. Effects of the top scoring compounds were investigated in a cell model that stably expresses Z-variant alpha 1-antitrypsin and in PiZ mice expressing Z-variant human alpha 1-antitrypsin (Z-hAAT), encoded by SERPINA1*E342K. 4','5-(Methylenedioxy)-2-nitrocinnamic acid was predicted to bind cleaved alpha 1-antitrypsin at the polymerization interface, and observed to co-localize with Z-hAAT, increase Z-hAAT degradation, inhibit intracellular accumulation of Z-hAAT, and alleviate liver fibrosis.

Desmoplasia and Detached Papillae in Early Esophageal Adenocarcinoma: A Histologic Study on Endoscopic Submucosal Dissection Specimens.

BACKGROUND: Desmoplasia and detached papillae were only rarely mentioned in intramucosal adenocarcinoma of esophagus or stomach. This study aimed to examine these two features in early esophageal adenocarcinoma. METHODS: All endoscopic submucosal dissections specimens performed for Barrett's esophagus neoplasm during the year 2013 to 2016 were reviewed. These 44 cases included in this study were eight Barrett's esophagus with high-grade dysplasia, 21 intramucosal adenocarcinoma, and 15 submucosally or beyond invasive adenocarcinoma. RESULTS: Desmoplasia occurred in 73% submucosally or beyond invasive adenocarcinoma, higher than intramucosal adenocarcinoma (24%) and high-grade dysplasia (0%) (P < 0.00001 for each). The frequency of detached papillae in intramucosal adenocarcinoma and submucosally or beyond invasive adenocarcinoma specimens was 71.4% and 73.3%, higher than high-grade dysplasia (0%, P < 0.0001 for both). Univariate analysis identified desmoplasia as risk factors for lymphovascular invasion in intramucosal adenocarcinoma specimens (odds ratio 12, P = 0.048), and desmoplasia and tumor thickness for lymphovascular invasion in intramucosal adenocarcinoma and submucosally or beyond invasive adenocarcinoma specimens combined (odds ratio 9.0, P = 0.005; odds ratio 2.7, P = 0.01, respectively). Age, gender, the largest dimension and the average thickness of endoscopic submucosal dissection specimens, tumor size, detached papillae, and poor differentiation were not associated with lymphovascular invasion (P ≥ 0.05 for all). Multivariate analysis confirmed that only desmoplasia was predictive of lymphovascular invasion (odds ratio 8.0, P = 0.02) in intramucosal adenocarcinoma and submucosally or beyond invasive adenocarcinoma specimens combined. CONCLUSIONS: In conclusion, desmoplasia occurs in about a quarter of esophageal intramucosal adenocarcinomas and three quarters of submucosally or beyond invasive adenocarcinomas, and is associated with lymphovascular invasion in early esophageal adenocarcinoma.

Steatohepatitic Variant of Hepatocellular Carcinoma: A Focused Review.

The incidence of hepatocellular carcinoma (HCC) has steadily increased over the past three decades and currently ranks as the fifth most common cancer worldwide. Likewise, non-alcoholic fatty liver disease (NAFLD), a known risk factor for the development of HCC, has emerged as the most common liver disease in Western countries. The underlying pathogenesis of NAFLD-related HCC remains unclear. The steatohepatitic variant of HCC (SH-HCC) typically presents in patients with metabolic risk factors and either cirrhotic or non-cirrhotic NAFLD and shares many of the histological features found in non-alcoholic steatohepatitis (NASH). Given their similar morphological features, distinguishing SH-HCC from background fatty liver can be a diagnostic challenge. Immunohistochemical studies to characterize and assist in the diagnosis are relatively limited. Whether the steatotic phenotype of SH-HCC results from the tumor's adaptive response to an environment rich in fatty acids or from an independent pathogenic pathway remains to be seen. This review aims to summarize what is currently known regarding the pathogenesis and clinicopathological features of SH-HCC.

Common Inflammatory Disorders and Neoplasia of the Ileal Pouch: A Review of Histopathology.

Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure after proctocolectomy in patients with ulcerative colitis (UC) who require colectomy. The ileal pouch is susceptible to a variety of insults including mechanical injury, ischemia, fecal stasis, and infectious agents. In addition, the development of recurrent and idiopathic inflammatory bowel disease and neoplasia may occur in the ileal pouch. Although clinical, endoscopic, and radiographic examination can diagnose many ileal pouch diseases, histologic examination plays an essential role in diagnosis and management, particularly in cases with antibiotic refractory chronic pouchitis and pouch neoplasia.

Clinical significance and management of Barrett's esophagus with epithelial changes indefinite for dysplasia.

Barrett's esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND.

An atypical case of chronic diarrhoea: olmesartan-induced sprue-like enteropathy.

Olmesartan use has been associated with chronic diarrhoea and weight loss due to severe sprue-like enteropathy, yet this is still not well known among clinicians. We present the unique case of an 84-year-old Filipino woman diagnosed with olmesartan-induced sprue-like enteropathy after an extensive work up for chronic diarrhoea, and without improvement despite multiple empiric treatments for nearly 15 months. Withdrawal of olmesartan resulted in clinical and histological improvement. This case provides further evidence for olmesartan-induced sprue-like enteropathy, and emphasises the importance of its awareness and recognition among gastroenterologists and primary care physicians alike.

Hirschsprung disease and use of calretinin in inadequate rectal suction biopsies.

CONTEXT: Up to 17% of all rectal suction biopsies performed in the evaluation of Hirschsprung disease are considered inadequate. In most instances, inadequate biopsies contain too little submucosa or are taken within the anal transition zone. OBJECTIVES: To examine the utility of calretinin stain in the workup of inadequate biopsies for patients with clinical suspicion of Hirschsprung disease. DESIGN: A retrospective analysis was conducted of all rectal suction biopsies performed in the evaluation of Hirschsprung disease during the previous 12 years that were considered "inadequate." Seventeen cases were identified, and Hirschsprung disease status was determined by clinical or surgical follow-up. Immunohistochemistry for calretinin was performed for all cases containing columnar mucosa, which were evaluated without knowledge of clinical course. RESULTS: All 12 patients without Hirschsprung disease had calretinin-positive nerve fibers in the lamina propria or muscularis mucosae, and all 5 patients with Hirschsprung disease had no calretinin staining of nerves. CONCLUSIONS: In this retrospective series, calretinin immunohistochemistry correctly predicted outcome in all instances. Although the gold standard for the diagnosis of Hirschsprung disease in rectal suction biopsies remains the evaluation of ganglion cells in a hematoxylin-eosin staining with sufficient submucosa, calretinin immunohistochemistry is quite helpful in triaging further workup based on clinical suspicion.