2024 Upper Gastrointestinal Tract Zoom Pathology Lectorial PDF

Upper Gastrointestinal Tract Zoom Pathology Lectorial 2024 Dr. Suja Pillai Pathology Schedule for second half of the year Zoom link https://uqz.zoom.us/j/83535455952 Week Pathology Zoom Lectorials Multi...

Upper Gastrointestinal Tract Zoom Pathology Lectorial 2024 Dr. Suja Pillai Pathology Schedule for second half of the year Zoom link https://uqz.zoom.us/j/83535455952 Week Pathology Zoom Lectorials Multidisciplinary practicals 20 Upper GIT No MDP 21 Intestines 1 No MDP Nutrition, 22 Intestines 2 Upper GI Gastrointestinal 23 No lectorial Intestines 1 and Metabolism 24 Liver gall bladder Intestines 2 &pancreas 25 No lectorial Liver gall bladder &pancreas 26 No lectorial No MDP 27 No lectorial No MDP Integumentary System 28 Skin No MDP 29 No lectorial Skin&Breast 30 Diseases of bones No MDP 31 No lectorial Diseases of bones Musculoskeletal 32 Diseases of joints No MDP System 33 No lectorial Diseases of joints 34 No lectorial No MDP 35 Revision Revision Learning Objectives Mouth Sjogren syndrome Pleomorphic adenoma Leukoplakia Oral cancer Oesophagus Congenital and acquired diseases of the oesophagus Neoplasms Stomach Gastritis Peptic ulcer disease Neoplasms Basics Mouth Oral mucosa Keratin Stratified squamous epithelium Stratified squamous epithelium The lining mucosa of the oral cavity, which The epithelial surface hard palate, gingiva and in is present on the lips, buccal mucosa, some regions of specialized mucosa on the alveolar mucosa, soft palate, underside of dorsum of the tongue the tongue, and floor of the mouth, has an epithelium that is usually nonkeratinized Sialolithiasis Formation of stone in salivary ducts Sjogren syndrome Diagnosis 2 types  Detection  Chronic inflammatory autoimmune disease -Primary of autoantibodies (ant  Mainly attacks lacrimal and salivary glands -Secondary i-SSA/Ro, ANA) Pathophysiology  Salivary gland biopsy. Extensive lymphocytic infiltrate Complications Corneal scarring, keratoconjunctivitis sicca B-cell lymphomas, such as MALT Dry eyes(Xerophthalmia) Dry mouth(Xerostomia) lymphoma Salivary Gland Tumor(Pleomorphic Adenoma) Microscopy :Three components Ductal cells Myoepithelial Matrix /stroma(myxoid, hyaline, or  Most common benign salivary chondroid). gland tumour  Occur in the parotid glands Malignant degeneration of a pleomorphic adenoma occurs, it is known as carcinoma ex pleomorphic adenoma. Ductal component Myoepithelial component Microscopy Stromal component Pleomorphic Adenoma Oral Premalignant lesions Definition(Leukoplakia)-Hyperkeratosis of the epithelium and mucous membranes of oral cavity Leukoplakia Speckled leukoerythroplakia Complication Erythroplakia Oral squamous cell carcinoma Dysplasia disorganized appearance of cells because of abnormal variations in size, shape, and arrangement. Architectural and cytological abnormalities such as 1. Pleomorphism 2. Increased nuclear cytoplasmic ratio 3. Increased and abnormal mitotic activity 4. Hyperchromatism Dysplasia++ + Invasion = Cancer Normal Mild Dysplasia Moderate Dysplasia Severe Dysplasia/ Dysplasia++ plus invasion Carcinoma in situ Anaplasia - Lack of differentiation Development of oral squamous cell carcinoma Normal oral epithelium Hyperkeratosis of oral Oral squamous cell Dysplasia of oral epithelium carcinoma epithelium Pleomorphism, Increased nuclear cytoplasmic ratio, Increased and abnormal mitotic activity, Hyperchromatism Normal Leukoplakia Oral squamous cell carcinoma  Keratin pearls Oral Squamous cell carcinoma TASK 1 Question 1 A 50-year-old lady presents with difficulty swallowing food and blurred vision. On physical examination you notice painless bilateral enlargement of the salivary glands. She is otherwise well. Anti SS-A and anti SS-B antibodies are positive. A salivary gland biopsy is performed and she is diagnosed with SJOGREN SYNDROME. a) What is Sjogren syndrome? Chronic autoimmune inflammatory disorder characterised by diminished lacrimal and salivary gland function with resultant dryness of the eyes and mouth What are the microscopic features of lymphocytes? (Try to visualize them in the microscopic image, they are key to the pathogenesis of Sjogren syndrome) lymphocytic infiltrate with formation of lymphoid follicles Patients with Sjogren syndrome are at risk of developing which malignancy? B-cell lymphomas TASK 1 Question 2 A 60-year-old female presents with a large, painless jaw mass, which she states has been present “for years”, and slowly increasing in size. The mass is surgically removed and assessed by a pathologist. She is diagnosed with PLEOMORPHIC ADENOMA. RBWH: X2983 Looking at the macroscopic images above, what features indicate that this tumour is benign? Pleomorphic adenoma is a well demarcated tumour Why pleomorphic adenoma is also called as mixed parotid tumour? The tumor has the following 3 components: A ductal component A myoepithelial cell component A stromal (mesenchymal) component Identification of these 3 components, which may vary quantitatively from one tumor to another, is essential to the recognition of pleomorphic adenoma. This tumor is also referred to as a benign mixed tumour. TASK 2 Question 1 LEUKOPLAKIA is a precancerous oral lesion. By Photo uploaded by: dozenist. [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC BY-SA 2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0- 1.0)], via Wikimedia Commons How do you clinically define leukoplakia? Leukoplakia as defined by the World Health Organization is “a white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease.” How is it different from erythroplakia Erythroplakia, which is a red, velvety, possibly eroded area within the oral cavity that usually remains level with or may be slightly depressed in relation to the surrounding mucosa. The epithelium in such lesions tends to be markedly atypical, and the risk of malignant transformation is much higher than is leukoplakia. TASK 2 Question 2 The following images depict ORAL SQUAMOUS CELL CARCINOMA. By Welleschik (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons What are the risk factors for oral squamous cell carcinoma? Tobacco use, alcohol, chewing betel nut, sun radiation exposure, human papilloma virus Describe the micrograph of oral squamous cell carcinoma. Keratin Pearls Outline the stepwise pathogenesis of oral squamous cell carcinoma (ensure you can explain the concept of dysplasia) Normal squamous epithelium -> hyperkeratosis -> mild/moderate dysplasia - > severe dysplasia/CIS -> SCC. Dysplasia or cancer Oesophagus Layers of the Gastrointestinal Tract 1.The mucosa 2: The submucosa(Meissner’s plexus) 3: The muscularis propria (light pink) is composed of an inner circular and outer longitudinal layer.(Myenteric/Auerbach’s plexus) 4: The serosa (dark pink) is composed of mesothelial tissue 1.The mucosa 2: The submucosa(Meissner’s plexus) 3: The muscularis propria (light pink) is composed of an inner circular and outer longitudinal layer.(Myenteric/Auerbach’s plexus) 4: The serosa (dark pink) is composed of mesothelial tissue  Submucosal glands Oesophagus Histology Congenital conditions affecting oesophagus Clinical Features (Oesophageal Atresia) -Polyhydramnios(mother) -Frothing  Congenital defect in which the -Choking upper esophagus is not connected to the -Aspiration pneumonia lower esophagus, ending blindly instead.  Caused by the abnormal development of the tracheoesophageal septum. Esophageal Atresia/Tracheoesophageal Fistula Motility disorder affecting oesophagus Esophageal motility refers to contractions occurring in the esophagus, which propel the food bolus forward toward the stomach. When contractions in the esophagus become irregular, unsynchronized or absent, the patient is said to have esophageal dysmotility.  Nutcracker esophagus  Diffuse esophageal spasm  Hypertensive lower esophageal sphincter  Achalasia spiral appearance rosary bead Achalasia  Characterized by inadequate relaxation of the lower esophageal sphincter (LES) and non- peristaltic contractions in the distal two-thirds of the esophagus  Caused by a loss of ganglion cells in the myenteric plexus of the oesophagus 2 Types Primary Secondary Complications Aspiration pneumonia Megaesophagus Increased risk of esophageal cancer Triad of incomplete lower esophageal sphincter (LES) relaxation, increased LES tone, and esophageal aperistalsis. Dilation of upper oesophagus Oesophageal diverticulum Esophageal diverticula are abnormal pouches that arise from the wall of the esophagus. Esophageal diverticula can be caused by either an underlying motility disorder that exerts high intraluminal pressures on a weak esophageal wall or from forces pulling on the outside of the esophagus Esophageal Webs Esophageal Rings  Semi circumferential, upper oesophagus  Circumferential thin membranes that  Composed of a fibrovascular connective tissue typically occur in the lower/distal and overlying epithelium. oesophagus  Composed of mucosa, submucosa and sometimes muscularis propria  3 Types A,B,C Seen in Plummer-Vinson syndrome. When the luminal diameter is less than 13 mm, at which point the B-ring is called a Schatzki ring. Oesophageal Obstruction Complication  Necrosis  Perforation  Aspiration into the lungs causing bronchopneumonia  Spread of infection into surrounding tissues leading to mediastinitis, pericarditis, pleuritis etc. Oesophageal varices Portal hypertension refers to a pathological elevation of portal venous pressure resulting from obstructions in portal blood flow  Prehepatic  Hepatic  Post-hepatic Dilated submucosal veins Complication Oesophageal variceal Portosystemic anastomoses Hemorrhage(massive hematemesis) Esophageal Tears Sudden and severe rise in the Mallory Weiss tear esophageal intraluminal pressure results in tearing of the esophageal mucous membrane, as well as the submucosal arteries and veins. Longitudinal tear; limited to mucosa and submucosa Boerhaave syndrome-rupture of all layers of the esophageal wall (transmural perforation) Gastroesophageal reflux disease (GERD) Chronic condition in which stomach contents flow back into the esophagus, causing irritation to the Risk factors mucosa.  Obesity  Fatty foods  Caffeinated or carbonated beverages Cause- Lower oesophageal sphincter (LES)  Alcohol incompetence  Smoking  Drugs Complications: Oesophagitis, Oesophageal ulcer, Oesophageal stricture, Barrett oesophagus, and oesophageal adenocarcinoma Barrett’s Oesophagus A metaplastic, columnar, glandular, intestine-like mucosa with brush border and goblet cells replaces the normal stratified squamous epithelium of the distal esophagus Dysplasia in Barrett’s oesophagus Adenocarcinoma Oesophagus Squamous Cell Carcinoma Oesophagus (SCC) -Most common type of oesophageal cancer worldwide. -SCC occurs in the upper/middle part of oesophagus Risk Factors  Alcohol  Tobacco  Caustic injury  Achalasia  Radiation exposure  Carcinogen (acetyl aldehyde)  HPV non-keratinising squamous epithelium lamina propria. muscularis mucosae Submucosal glands TASK 3 Question 1 Match the following clinical scenarios (A) to (D) with the corresponding pots (1) to (4) 1 2 A 32-year-old man complains of difficulty swallowing and a tendency to regurgitate his food. Manometric studies of the oesophagus show a complete absence of peristalsis, failure of the lower oesophageal sphincter to relax upon swallowing, and increased intraoesophageal pressure. 2 The mother of a newborn boy is alarmed that her baby regurgitates at every feeding. An endoscopic examination reveals that the child’s oesophagus is almost completely RB X4153B PA X3702 occluded 1 3 4 A 58-year-old woman is brought to the emergency department 4 hours after vomiting blood and experiencing bloody stools. The patient was diagnosed with alcoholic cirrhosis 2 years ago. 3 A 30-year-old man has sudden onset of hematemesis after a weekend in which he consumed large amounts of alcohol. The bleeding stops, but he has another episode under similar circumstances 1 month later. 4 RBWH: X522C PA: X3879 TASK 3 Question 2 Match the features with the most appropriate clinical condition: Oesophageal Obstruction Condition Features 1. Diffuse oesophageal spasm A. Mucosal semi-circumferential protrusion 2. Zenker diverticulum B. Repetitive distal oesophageal contractions 3. Oesophageal mucosal web C. Outpouching above upper oesophageal sphincter. 4. Oesophageal (Schatzki) ring D. Mucosal/submucosal circumferential protrusion 1=B 2=C 3=A 4=D TASK 4 Question 1 A 50-year-old male has a twenty-year history of gastro-oesophageal reflux symptoms. He presents to the GP to discuss the problem for the first time. His GP places him on a proton-pump inhibitor and arranges an upper gastrointestinal endoscopy. The biopsy of the gastroesophageal junction demonstrates the following: What type of cellular adaptation is By Nephron (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by- sa/3.0) or GFDL evident in the microscopy above? (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons Metaplasia What is the name of the condition depicted? Barrett Oesophagus What is the major risk factor for this condition? Gastro-oesophageal reflux disease What malignancy is this patient at risk of developing? Oesophageal adenocarcinoma TASK 4 Question 2 The same gentleman from question 1 does not take his medication and decides not to worry about his reflux even through his GP has recommended treatment and surveillance based on his endoscopy result. His oesophagus then undergoes the following changes: a) Describe the pathology in the patient’s oesophagus. Dysplasia in Barrett oesophagus TASK 4 Question 3 At age 70 the same patient goes back to his GP with dysphagia and weight loss. He finally agrees to undergo another upper gastrointestinal endoscopy, and the following lesion is found: a) What is the likely diagnosis based on RBWH: X2561 the macroscopic image? Oesophageal adenocarcinoma b) How does the location of the lesion point to the likely diagnosis? It usually arises in the distal one-third of the oesophagus, as most oesophageal adenocarcinomas arise from Barrett oesophagus STOMACH  Gastritis Gastropathy Inflammation of the gastric mucosa When inflammation is rare or absent Cause  Infection (H.pylori gastritis)  Direct injury  Part of a systemic inflammatory disease 2types Acute Chronic Atrophic(Autoimmune/Type A) Non atrophic(H.Pylori/Type B) Special forms Autoimmune Gastritis Autoimmune disease that attacks parietal cells, resulting in hypochlorhydria and decreased production of intrinsic factor Affects the corpus and fundus and spares the antrum Diffuse atrophy occurs in autoimmune gastritis Complications  Pernicious anaemia  Carcinoid tumours  Gastric Adenocarcinoma Autoantibodies to parietal cell components, most prominently the H+,K+-ATPase, or proton pump, and intrinsic factor are present in up to 80% of patients with autoimmune gastritis. H Pylori Gastritis Clinical outcomes are associated with H.Pylori  Antral-predominant infection -Chronic gastritis  Corpus-predominant infection -Gastric ulcer  Multifocal --Deuodenal ulcer -Gastric cancer Intraepithelial neutrophils and subepithelial plasma cells are characteristic of H. pylori gastritis. Gastritis, followed by gastric atrophy (loss of glandular structure) and progressing to intestinal metaplasia, dysplasia, and finally carcinoma  Microscopy Chronic Gastritis Lymphoid follicles Intestinal metaplasia Paneth cells Gastric atrophy Summary H. pylori–Associated Autoimmune Location Antrum Body H. pylori–Associated Autoimmune Inflammatory infiltrate Neutrophils, subepithelial Lymphocytes, macrophages Location Antrum plasma cells Body Inflammatory infiltrate Neutrophils, Lymphocytes, macrophages subepithelial plasma Acid production Increased cells to slightly decreased Decreased Acid production Increased to slightly Decreased Gastrin decreased Normal to decreased Increased Gastrin Other lesions Normal to decreased Hyperplastic/inflammatory Increased Neuroendocrine hyperplasia Other lesions polyps Hyperplastic/inflammat Neuroendocrine hyperplasia ory polyps + + Serology Antibodies to H. pylori Antibodies to parietal cells (H ,K -ATPase, + + Serology Antibodies to H. pylori intrinsic factor) Antibodies to parietal cells (H ,K - ATPase, intrinsic factor) Sequelae Peptic ulcer, adenocarcinoma, Atrophy, pernicious anemia, Sequelae Peptic ulcer, MALToma Atrophy, pernicious anemia, adenocarcinoma, carcinoid tumor adenocarcinoma, adenocarcinoma, carcinoid tumor MALToma Associations Associations LowLow socioeconomic status, Autoimmune socioeconomic Autoimmune disease, disease, thyroiditis, diabetes thyroiditis, poverty, residence status, poverty,in rural mellitus, diabetes GravesGraves mellitus, diseasedisease areas residence in rural areas Peptic ulcer disease Defect in the gastric or duodenal mucosa that reaches Etiology the muscularis mucosae/submucosa  H. Pylori  Gastric ulcer: ulcer of the gastric mucosa, typically  Nonsteroidal anti- located along the lesser curvature in the inflammatory drug use transitional portion between the corpus and  Zollinger-Ellison Syndrome antrum  Viral infection  Duodenal ulcer: ulcer of the duodenal mucosa, usually located on the anterior or posterior wall of the duodenal bulb ulcer punched out appearance Peptic ulcer Complications Malignant  Haemorrhage transformation does  Penetration (confined not occur in duodenal perforation) ulcers and is  Free perforation extremely rare in  Gastric outlet obstruction gastric ulcers.  Recurrence Acute, or stress, ulcers are most commonly encountered in patients with shock, burns, sepsis, intracranial conditions, and aspirin use. Neoplasm Gastric Adenomas Gastric Adenomas almost always occur on a background of chronic gastritis with atrophy and intestinal metaplasia. Gastric cancer Risk factors  Helicobacter pylori infection  Autoimmune atrophic gastritis  Smoking  Diet(smoked, dried, and preserved food)  Gastric polyps  Genetic factors Histological Types  Gastric adenocarcinoma  Gastric lymphomas  Carcinoid tumors  Gastrointestinal stromal tumor Lauren’s classification Morphologically divided into 4 types (Borrmann classification) Intestinal type Gastric Diffuse type adenocarcinoma Signet ring Diffuse Gastric adenocarcinoma Intestinal type Diffuse type  Common type  Not common  Affects older people  Affects young people  Associated with environmental  Associated with mutations in E- factors cadherin  Antrum and lesser curvature of the  Develop throughout the stomach stomach (including the cardia)  Characterized by cohesive neoplastic cells  Characterised by absence of cell that form glandlike tubular cohesion so that individual cells structures(retain E-cadherin function) infiltrate and thicken the stomach wall without forming a discrete mass Routes of spread Local invasion of adjacent structures Hematogenous spread Lymphangitic spread Virchow node: left supraclavicular lymph node metastasis Sister Mary Joseph node: periumbilical lymph node metastasis (subcutaneous) Peritoneal Spread Krukenberg tumour Blumer shelf (direct seeding to the pouch of Douglas) Virchow node Sister Mary Joseph node Krukenberg tumour TASK 5 Question 1 A 65-year-old male presents to his GP with persistent epigastric pain, which improves with antacids. He admits he takes regular anti- inflammatory medications for joint pain. He has not experienced any haematemesis or melaena. His GP suspects GASTRITIS. Define gastritis. What would you expect to see on microscopy? Inflammation of gastric mucosa – inflammatory cells. Histologically, gastritis is an inflammatory process thus neutrophils will be present acutely. What is the likely mechanism that led to gastritis in this case? NSAIDs inhibit COX pathway and thus inhibit prostaglandin synthesis. Prostaglandins stimulate gastric defence mechanisms (mucus, bicarbonate and phospholipid secretion, mucosal blood flow, epithelial healing. Thus NSAID use promotes gastric irritation due to acidic environment. What are your other differential diagnoses for this patient? Gastritis, peptic ulcer, GORD What is autoimmune gastritis? – Genetically influenced – -CD4+ T cells injure parietal cells – -Parietal cell atrophy occurs in the body and fundus of the stomach – -Loss of parietal cells leads to reduced gastric acid and intrinsic factor secretion – -Reduced acid stimulates gastrin release – -Hypergastrinemia causes hyperplasia of antral gastrin-producing G-cells – -Lack of intrinsic factor causes vitamin B12 deficiency and megaloblastic anaemia TASK 5 Question 2 A 55-year-old female presents to the emergency department following one episode of bright red haematemesis. On further history she has had burning epigastric pain after meals and in the middle of the night for months. Representative pots are shown. a) What is the diagnosis? Peptic ulcer Describe the macroscopic features in pot RBWH: X2555 PAH: X4411 specimens which support your diagnosis. Macro – punched out appearance with clean base; micro - Sharply demarcated gastric ulcer demonstrating normal gastric mucosa (left) which falls away to a deep ulcer containing inflammatory infiltrates, granulation tissue, and possibly fibrosis. What is the likely causative organism? Helicobacter pylori List four virulence factors for the causative organism Flagella, Urease, Adhesins, Toxins TASK 6 Question 1 2 pots are provided showing 2 subtypes of GASTRIC ADENOCARCINOMA. Intestinal-type adenocarcinoma Diffuse infiltrative adenocarcinoma a) Name each subtype. b) What are their morphological differences (both gross and microscopic)? Macro = elevated mass with heaped boarders; micro = gland forming cells Macro = thickened gastric wall, loss of rugal folds; Micro = signet ring cells Which subtype is associated with loss of E-cadherin? Diffuse infilterating a) How does E-cadherin presence/absence influence their morphology? E-cadherin is a cell adhesion protein. As such, intestinal-type adenocarcinomas (which retain E-cadherin function) proliferate by growing as a single mass; in contrast, the diffuse infiltrating type (which has lost E- cadherin) is composed of discohesive cells which do not form glands. Instead they have large mucin vacuoles that expand cytoplasm and push the nucleus to the periphery, forming signet cells. TASK 6 Question 2 RBWH: X99A A 65-year-old male presents to his GP with fatigue and weight loss. On examination the GP notices an umbilical nodule. The patient dies a few months later. Autopsy showed GASTRIC ADENOCARCINOMA (pot specimen and microscopy below). a) What type of gastric adenocarcinoma is present based on the images? Diffuse infiltrative adenocarcinoma b) Outline the clinical signs that manifest when gastric adenocarcinoma metastasises. Lymphatic Spread: -Sister Mary Joseph Node (umbilical) -Virchow’s Node (left supraclavicular) Peritoneal Spread: -Kruekenberg Tumour (ovary) -Blumer’s shelf (rectal mass on DRE) Email: [email protected]