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3.Montgomery.Nonneoplastic Gastric Pathology Nonneoplastic Gastric Disclosure Statement Pathology Dr. Montgomery reports no relevant financial (Will cheat a Bit and Include relationships with commercial interests. Endocrine Lesions) Elizabeth Montgomery Stomach! We will begin with a whirwind tour of the First, a few pitfalls things that we can encounter in gastric biopsies and then review a focused case with differential diagnosis Pitfall – erosive gastropathy – A Few Benign Pitfalls note that the reparative glands respect the muscularis mucosae Crushed mucosa with sloughed mucous border. neck cells Erosive gastritis/gastropathy including iron pill gastritis “Signet cell change” Gastric Xanthoma Pitfall - Iron pill gastritis Pitfall - Iron pill gastritis with reactive changes with reactive changes Pitfall - Iron pill gatritis with reactive changes – iron stain Pitfall - signet cell change in ischemic columnar mucosa; cells lose their cohesion and slough into the lumen whilst rounding up Remember that signet cell change is very different from the in situ signet ring cell cancers in patients with CDH1 (the gene encoding for e-cadherin) germline mutations Pitfall - signet cell change in ischemic columnar mucosa; cells retain E-Cadherin expression Pitfall – crushed mucosa with prominent mucus neck cells – note the the sloughed single cells are not within lamina propria but floating and seen in gland lumina Pitfall – crushed mucosa with prominent mucus neck cells – note the the sloughed single cells are not within lamina propria but floating and seen in gland lumina Pitfall – crushed mucosa with prominent mucus neck cells – note the the sloughed single cells are not within lamina propria but floating and seen in gland lumina The real thing – signet cell Pitfall – crushed mucosa with carcinoma - the bad cells are firmly prominent mucus neck cells – note in the lamina propria so not seen the sloughed in the lumina single cells are seen in gland lumina – oil immersion (bad idea) Gastric xanthoma Gastric xanthoma, PAS Mucosal calcinosis – seen in patients with renal failure or other disorders of calcium metabolism such as And now a whirlwind of things parathyroid adenomas we encounter on biopsies.. Some rare and some common Calcium pill gastritis – same pattern with doxycycline Proto pump inhibitor effect Sarcina ventriculi Patient with diabetes and slow gastric emptying – note exudate and organisms at low power Sarcina ventriculi Sarcina ventriculi gastritis Gram positive, anaerobic, sugar-fermenting bacterium, S. ventriculi was first observed in the human stomach in 1842 by Goodsir . Readily found in soil and is known to cause a similar type of gastric injury in animals. Delayed gastric emptying and carbohydrate stasis in association with acidic gastric juices may provide an ideal culture medium #,*,+*-"1*#2*1.-2(.,'06#* 0.5- #7#4*#,/11)+',#- )#(#4#--&'01 !#0%*-#.0(#-*1,1*-2)'(#120.*-2'1 #,*,+*-"1*#2*1.-2(.,'06#* 0.5- #7#4*#,/11)+',#- )#(#4#--&'01 !#0%*-#.0(#-*1,1*-2)'(#120.*- Lymphocytic gastritis – Most Sarcina Ventriculi gastritis common association – Celiac disease followed by H. Pylori Studied patients all had underlying delayed gastric emptying (one had a bezoar) from diabetic neuropathy, narcotic use, and pyloric stenosis secondary to malignancy The organism may simply colonize pre-existing lesions but there are too few cases to draw firm conclusions as to whether the organism is truly a pathogen. Packets of 4, 8 or more cells with characteristic flattening Lam-Himlin D, Tsiatis AC, Montgomery E, Pai RK, Brown JA, Razavi M, Lamps L, Eshleman JR, Bhagavan B, Anders RA. Sarcina organisms in the gastrointestinal tract: a clinicopathologic and molecular study. Am J Surg Pathol. 2011 Nov;35(11):1700-5. Collagenous Gastritis Associated with various autoimmune diseases in both children and adults We have seen it associated with medications (eg Benicar/Olmesartan) Early studies proposed 2 clinicopathologic subtypes: (1) children (18 y of age or younger) presenting with severe anemia, nodular gastric mucosa, and isolated gastric disease; and (2) adults with chronic watery diarrhea that is associated with diffuse collagenous involvement of the gastrointestinal tract. Lymphocytic gastritis – Most Ma C, Park JY, Montgomery EA, Arnold CA, McDonald OG, Liu TC, Salaria SN, Limketkai BN, McGrath KM, Musahl T, Singhi AD. A Comparative Clinicopathologic Study of Collagenous Gastritis in Children and Adults: The Same Disorder common association – Celiac With Associated Immune-mediated Diseases. Am J Surg Pathol. 2015 Apr 10. [Epub ahead of print] PubMed PMID: disease followed by H. Pylori 25871617. Collagenous gastritis – poorly understood and sometimes resolves by itself – presents with watery diarrhea just like collagenous colitis Collagenous gastritis associated with autoimmune gastritis Collagenous gastritis in gastric body. Is something missing (you betcha – parietal cells) Collagenous gastritis associated with autoimmune gastritis – chromogranin stain showing enterochromaffin like (ECL) cell hyperplasia Collagenous gastritis associated with autoimmune gastritis Granulomatous gastritis – pattern – can be Crohns disease but always requires correlation with clinical findings Cytomegalovirus gastritis – note that the EPITHELIAL cells are often affected in the stomach Cytomegalovirus gastritis – the monocyte-rich inflammation can mimic a lymphoma Russell body gastritis – usually a curious incidental findings and only sometimes associated with plasma cell disorders Syphilis Gastritis Russell body gastritis, PAS/AB stain Not well studied and correlation with HIV status is not well established in the literature (which consists mostly of case reports) The key is that is tends to present in young adults with diffuse erosive gastritis or lesions that mimic carcinoma and lymphoma Vintage images of syphilis gastritis courtesy of the late Jack Yardley Epstein Barr virus Gastritis Epstein Barr virus Epstein Barr virus gastritis – mimics gastritis – mimics lymphoma lymphoma EBV in situ EBV gastritis – note hybridization nuclear hybridization in the exuberant mixed lymphoid infiltrate Measles Measles gastritis!!!! gastritis Measles gastritis Case A 68 year old woman with dyspepsia underwent upper endoscopy and had some gastric biopsies. The endoscopist thought the mucosa was atrophic and also saw a polyp. Antrum – 68 yo woman Body Body polyp Diagnosis Autoimmune gastritis Hyperplastic polyp Esophagus, Stomach, and Duodenum: Normal Antral Mucosa with Gastric Lumen (LUM), Normal Anatomic Outlines and Relationships Foveolae (FOV), and Antral Glands (AG) Indicated H&E Mucus (PAS) Normal Oxyntic Mucosa with Foveolae (FOV), Major Endocrine Cell Types of the Stomach and Parietal Cells (PC), and Chief Cells (CC) Indicated Their Products - Immunostain Demonstrations H&E Stain Mucus Stain (PAS) A few Comments on Helicobacter pylori Gastritis Two Australians win Nobel Prize in Medicine Awarded for work on peptic ulcer disease Helicobacter pylori: Curved Organisms (HP) with Flagellae Over Gastric Epithelium R. Warren B. Marshall Pathology GI Medicine & Light Microscopy Electron Microscopy Microbiology Variant form – Helicobacter Prevalence of Helicobacter pylori Infection in heilmannii Reacts with H. Developing vs. Developed Countries pylri immunostain Similar clinical profile to H pylori Pediatric cases possible over- represented Aliment Pharmacol Ther 1995;9(Supp2):33 Consequences of H. pylori infection Duodenal and “Pre-Pyloric” Ulcers Many are asymptomatic “dyspepsia” Peptic ulcer Atrophy and intestinal metaplasia of mucosa Increased risk for intestinal type adenocarcinoma MALT lymphoma Link to autoimmune gastritis in susceptible host Duodenal Ulcer with Brunner Gland (BG) Hyperplasia, Eradication of H. Pylori in Recurrent Duodenal Ulcer Pancreatic Penetration and Exposed Artery NEJM 328 : 308-312, 1993 Benign Gastric Ulcer - Lesser Curve, Transitional Zone Environmental Metaplastic Atrophic Gastritis • Suspected causative factors: - H. pylori infection - Dietary: High salt; smoked foods; nitrates; poor fruit and vegetable intake Antrectomy - Others: Specimen Smoking H. Pylori associated Metaplastic Atrophic Gastritis H. Pylori Organisms Have Specific Affinity for Gastric (Stemmermann’s Technique; stained for alkaline phosphatase ) Mucous Cells But Not Intestinal Absorptive Cells Advanced Early Red areas = intestinalization Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M; Japan Gast Study Group. Effect of eradication Carcinoma in Environmental Metaplastic of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised Atrophic Gastritis (EMAG) controlled trial. Lancet. 2008 Aug 2;372(9636):392-7. Metaplastic Atrophic Gastritis (MAG) Autoimmune vs. H.pylori Types Autoimmune gastritis Autoimmune H. pylori Autoimmune vs. Environmental Autoimmune MAG (AMAG) Metaplastic Atrophic Gastritis • Etiology/ - Inherited predisposition Pathogenesis: - Autoimmune-induced damage Parietal cell antibodies Intrinsic factor antibody - H. pylori organisms usually absent • Pathology: - Body (ONLY!) DIFFUSE METAPLASIA; mucosa thin Loss of oxyntic glands (“atrophy”) - Antrum - NO METAPLASIA; hyperplasia - Endocrine Autoimmune H. Pylori G-cell hyperplasia Red areas = intestinalization ECL cell hyperplasia Autoimmune Metaplastic Atrophic Autoimmune Metaplastic Atrophic Gastritis Gastritis (AMAG) - Autopsy (AMAG) vs. Normal Mucosa AMAG Normal Oxyntic Mucosa Oxyntic Mucosa: Autoimmune Metaplastic
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