Pathology Lecture 2024 Upper GI Pathology.pdf

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Upper GI Pathology Class Year 2 Course Pathology Lecturer Dr Katherine Sheehan Date 09th September 2024 Barrett’s Oesophagus “New” junction between s...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Upper GI Pathology Class Year 2 Course Pathology Lecturer Dr Katherine Sheehan Date 09th September 2024 Barrett’s Oesophagus “New” junction between squamous and glandular mucosa Glandular mucosa Gastroenterologist can see this change during an Upper GI Endoscopy:  Barrett’s Oesophagus Persistent reflux – 3 – 12% of patients with symptomatic reflux May become dysplastic – Risk of developing adenocarcinoma 0.5% per year Surveillance endoscopy required for screening Goblet cells Oesophageal Tumours  Oesophageal Tumours Benign – Leiomyomas – Lipoma – Fibroma Malignant – Primary Most are epithelial – Squamous – Glandular Others: – GIST – Secondary  Clinical Features Presentation: – Dysphagia, worse for solids Diagnosis: – endoscopy and biopsy, radiology Gross appearance: – Polypoid – Ulcerating – Infiltrative Microscopy: – 70% squamous cell carcinoma – 25% adenocarcinoma  1) Squamous Cell Carcinoma (SCC) Most common site mid third of oesophagus Histology – Keratinizing/non keratinizing squamous lesions Symptoms – Dysphagia, odynophagia, weight loss  Risk Factors for SCC Oesophagus Dietary – Vitamin or trace metal deficiencies – High content of nitrites/nitrosamines Lifestyle – Alcohol – Tobacco Oesophageal disorders – Long-standing oesophagitis – Achalasia – Plummer-Vinson syndrome Genetic predisposition Long-standing coeliac disease Ectodermal dysplasia, epidermolysis bullosa  2) Adenocarcinoma 85-90% arise from Barrett’s oesophagus – Lower 1/3 of oesophagus Approx half of all oesophageal malignancies Mean age mid 60’s  Prognosis Spread of oesophageal cancer – Local – Lymph nodes – Blood Prognosis – depends on the stage and tumour type; presents late – 5 year survival local disease ~45%, nodal disease 25% and distant ~5%; Treatment – Neoadjuvant chemo RT – Oesophageal resection 40% – Stent – Adjuvant ChemoRadio Tx  Part B The Stomach  3D diagram of stomach wall; tubular depressions fromm the surface Scanning electron microscopy of gastric constitute the gastric pits with glands opening at the bottom of the pits. mucosa showing gastric pits x 1000 Histology: a text and atlas; Michael H. Ross et al; 3rd edition Inflammatory disorders of the stomach  Acute Gastritis Causes: – Alcohol – Drugs – NSAIDs (especially aspirin), steroids – Smoking – Corrosives eg. Paraquat, acids and alkalis – Stress: shock, trauma, ischaemia, burns – Uraemia – Gastric irradiation  Presentation: – Asymptomatic – Epigastric pain – N&V – Anaemia (from bleeding) – Haematemesis – Malaena – Histologically: – influx by neutrophils and oedema  Chronic gastritis The presence of chronic mucosal changes leading to a) mucosal atrophy and b) epithelial metaplasia, usually in the absence of erosions. The epithelial changes may become dysplastic, and constitute a background for developing carcinoma. 3 main types 1. Helicobacter-associated gastritis 2. Autoimmune chronic gastritis 3. Chemical / reflux gastritis Histologically: infiltration by lymphocytes and plasma cells  1) Helicobacter-associated gastritis Any age Antrum and corpus H. pylori: – Urease producing gram negative rod – Urease generates ammonia and protease – Epithelial damage – Acute and chronic inflammation – Lymphoid aggregates Diffuse antral gastritis, duodenal ulcers H. Pylori is seen in the superficial mucous layers (PAS stain) Multifocal atrophic gastritis; intestinal metaplasia gastric ulcers / cancer Increased risk of PUD and gastric cancer Diagnosis of Helicobacter-Associated Gastritis Urea breath test Biopsy Serology Culture  2) Autoimmune chronic gastritis Elderly – Autoantibodies against parietal cells and intrinsic factor Pernicious anaemia – Megaloblastic anaemia due to decreased vitamin B12 – Hypochlorhydria – increased risk of carcinoma; 2-4% – Also seen with other autoimmune disorders:- Hashimoto’s thyroiditis and Addison's disease Microscopically: – Gland destruction and mucosal atrophy of body and fundic mucosa, with less intense antral damage, leading to loss of acid production and intrinsic factor  3) Chemical / reflux gastritis -Reflux of duodenal fluid and bile -Commonest with previous gastric surgery -Microscopically: -Foveolar hyperplasia -Vascular ectasia -Fibromuscular lamina propria  Intestinal metaplasia -Metaplasia of gastric epithelium to small intestinal epithelium -Chronic gastritis -May become dysplastic -Increased risk of carcinoma -Surveillance endoscopy Photomicrographs of gastric intestinal metaplasia Hematoxylin and eosin; original magnification, ×400; inset, ×1,000  Peptic ulcer disease Due to gastric acid (acid-peptic juices) 5 sites – Duodenum (usually 1st part) – Stomach – Oesophagus (OGJ) – Gastric anastomosis – Meckel’s diverticulum (containing ectopic gastric mucosa) In patients with Zollinger-Ellison syndrome Ulcer: – A breach in the mucosa of the alimentary canal which extends through the muscularis mucosae into the submucosa or deeper.  Peptic ulcers – gross appearance -Round-oval, sharply punched-out -Relatively straight walls -Margins usually level with surrounding mucosa -Base is smooth and clean -Surrounding gastric mucosa: oedematous and reddened  Peptic ulcers – microscopic appearance Ulcer with fibrosis in the base and walls 3 zones: – Superficial slough – Chronically inflamed granulation tissue – Deep fibrous or collagenous scar Vessel walls within the scarred area are thickened by the inflammation and are occasionally thrombosed  Peptic ulcer disease Clinical Presentation: Gastric: – Epigastric pain, loss of appetite, weight loss – Nausea, vomiting, bloating, belching – Tends to be worse at night, 1-3 hours after food Duodenal: – pain may be relieved by eating / alkalis – Penetrating ulcers: pain referred to the back/chest/LUQ – Iron-deficiency anaemia – Haematemesis – Melaena – Perforation  Complications of peptic ulcer -Haemorrhage -Perforation -Penetration and intractable pain -Obstruction from oedema & scarring (Pyloric stenosis) -Malignant change (rare) -Often recur  Acute gastric ulcers – “Stress Ulcers” Usually develop from areas of acute erosive gastritis Severe stress or shock (Cushing’s, Curling’s) – Example: Extensive burns or trauma – Drugs can also cause acute gastric ulceration Microscopy; Range from erosion to ulceration – Ulcers are usually 20 years ago – due to reflux) -Peptic ulcer disease -Infection with H. Pylori -Intestinal metaplasia -Blood group A -Family history Gastric carcinoma Histology types: 1) Intestinal type 2) Diffuse type  Gastric cancer Spread -Local: duodenum, pancreas, retroperitoneum -Trans-coelomic: Krukenberg tumour of ovaries -Lymphatic: Virchow’s node (Supraclavicular / Troisier’s sign) -Haematogenous Prognosis -Depends on depth of invasion -Extent of nodal and distant metastases -5-year survival -Localized 70% -Regional 30% -Distal 5% -Overall 32%  Early gastric cancer -Confined to the mucosa or submucosa (regardless of the presence or absence of perigastric lymph node metastases) -Cure rate for intramucosal cancers = 93% -Cure rate with submucosal involvement = 80-89%  Gastrointestinal Stromal Tumours (GIST) Primary non-epithelial neoplasms Arise from interstitial cells of Cajal (control peristalsis) Can be solitary or multiple The majority of GISTs (95%) accompanied by a mutation of CD117 (c-kit) Tyrosine kinase receptor Tyrosine kinase inhibitor (Gleevec™) used as an agent to treat GISTs  Clinical features: Adults Abdominal pain Melaena Rarely obstruction cKIT The Mouth  Tumours of the Mouth Benign – Squamous papillomas / condyloma HPV 6 & 11 Malignant – Primary Most are primary – Floor of mouth, tongue, hard palate and base of tongue > 95% squamous cell carcinoma – Caused by things that irritate squamous mucosa – Tobacco and alcohol – Betel nuts – HPV 16, 18 – Sunlight and pipe smoking – Secondary Prognosis: – Best for lip (external and presents early)  Other Conditions of the Mouth Aphthous Ulcers – ? Crohn’s Xerostomia – Dry mouth – Causes Autoimmune Drugs Radiation  Other Conditions of the Mouth Glossitis - Deficiency states B12, iron Plummer-Vinson syndrome Leucoplakia - white plaque, can’t be removed by scraping - ? Premalignant: - Frequency of carcinoma in-situ or invasion 5% - Hairy Leukoplakia - HIV associated - EBV infection - Erythroplakia - Red, velvety area - Happens in the people that get oral cancer - Males - Smokers - 90% have associated carcinoma (or in situ carcinoma already).  Salivary Glands Major – Parotid – Submandibular – Sublingual Minor – Lip – Tongue (anywhere in the oral cavity)  Salivary Glands Ducts Glands – Serous Proteins, fluid – Mucinous mucin – Mixed Duct (cuboidal epithelium)  Pathology of Salivary glands Inflammation – Sialadenitis Can get – Sialorrhoea – Xerostomia Parotid – Viral – Suppurative – Staph aureus – Autoimmune – Sjogren’s Tumours – Benign – Malignant  Benign Tumours Usually painless swelling – Pleomorphic Adenoma (most common tumour of parotid) F>M Encapsulated: – Epithelial elements in mucoid and chondroid stroma Treatment by wide excision; Local recurrence is common – Difficult to excise – 25% with nucleation Malignant transformation may occur – 2% – Carcinoma ex pleomorphic adenoma – Warthin’s tumour (10%) Almost exclusively parotid Usually older males & smokers – 10% multifocal, 10% bilateral Double layer of epithelial cells on a dense lymphoid stroma Oncocytes and secretory cells +/- squamous metaplasia “Adenolymphoma” Pleomorphic adenoma Warthin tumour of the salivary gland  Malignant Tumours More common in minor glands Suggested by: – Rapid growth – Pain Types: – Mucoepidermoid Glands and squamous cells – Adenoid cystic carcinoma Cribriform, solid and tubular glands Perineural invasion – Acinic cell carcinoma Look like acinar cells – Carcinoma ex pleomorphic adenoma