Upper GI Pathology Year 2

Learning Outcomes

• Understand normal anatomy of the mouth, esophagus, and stomach.
• Recognize benign and malignant tumors of the oropharynx, esophagus, and stomach.
• Identify common conditions affecting the mouth and causes of salivary gland enlargement.
• Diagnose causes of esophagitis and gastritis.
• Define Barrett's esophagus.

Esophagus Anatomy

• Mucosa: Comprises squamous epithelium and lamina propria (loose connective tissue).
• Submucosa: Contains connective tissue, blood vessels, and nerves.
• Muscle Layer: Enables peristalsis.
• Adventitia: Connective tissue covering the esophagus.

Symptoms of Esophageal Disorders

• Dysphagia (difficulty swallowing) caused by:
  • Lesions in the lumen (e.g., foreign body, tumors)
  • Lesions in the wall (e.g., tumors, strictures)
  • Lesions outside the wall (e.g., tumors, aortic aneurysms)
  • Functional lesions (e.g., achalasia)

Anatomic Disorders of Esophagus

• Developmental Abnormalities:
  • Atresia/Fistula: Often linked to pulmonary issues.
• Acquired Abnormalities:
  • Diverticula:
    • True (involves all layers) vs. False (involves only mucosa/submucosa).
    • Pulsion: Pressure-induced; Traction: Local pathology-related.
  • Webs/Rings:
    • Webs: Thin mucosal folds (2-3mm).
    • Rings: Bands involving mucosa and submucosa.

Hiatus Hernia

• Affects 1-20% of adults.
• Separation of diaphragmatic crura into:
  • Sliding (95%): Movement of stomach through diaphragm.
  • Paraesophageal: Non-axial positioning.
  • Common Complications
    • Reflux: Particularly with sliding hernias, GERD is common due to the weakening of the LES.
    • Ulceration: Both types of hernias can result in ulcers within the herniated portion of the stomach due to the continuous acid exposure or mechanical irritation.

Esophageal Motor Disorders

• Achalasia:
  • Characterized by failure to relax with three key abnormalities:
    • Aperistalsis (lack of peristalsis)
    • Incomplete relaxation of lower esophageal sphincter during swallowing
    • Increased resting tone of lower esophageal sphincter

Causes of Achalasia

• Primary: Neural imbalance, degenerative conditions, diabetes.
• Secondary:
  • Infectious (Trypanosoma, Polio)
  • Infiltrative (tumors, amyloidosis, sarcoidosis)

Other Esophageal Abnormalities

• Esophageal Perforation:
  • Commonly due to instrumentation or severe vomiting (Mallory-Weiss tear).
• Esophageal Varices:
  • Dilated veins due to portal hypertension, prevalent in cirrhotic patients.

Inflammatory Disorders

• Infective:
  • Fungal (Candida albicans), viral (Herpes, CMV).
• Physical agents:
  • Radiation exposure, caustic substances.
• Reflux:
  • Contributing factors include abdominal pressure, hiatus hernia, smoking, and alcohol.

Reflux Esophagitis

• Histological features include:
  • Basal cell hyperplasia, eosinophils increase, elongated lamina propria papillae.

Esophagogastric Junction

• Location between esophagus and stomach.
• Contains:
  • Squamous Mucosa: Protective against physical trauma.
  • Glandular Mucosa: Produces mucus for acid protection.

Metaplasia in the Esophagus

• Chronic acid irritation leads to squamous to glandular mucosa transformation known as Barrett's esophagus.
• Long-segment Barrett's: Defined as more than 3 cm of columnar epithelium.

Barrett’s Oesophagus

• Characterized by a junction between squamous and glandular mucosa observed during Upper GI Endoscopy.
• Associated with persistent reflux in 3-12% of symptomatic patients.
• May develop dysplasia, leading to a risk of adenocarcinoma at approximately 0.5% per year.
• Requires regular surveillance endoscopy for early detection.

Oesophageal Tumours

• Benign tumours include leiomyomas, lipomas, and fibromas.
• Malignant primary tumours predominantly are epithelial, with squamous (70%) and glandular (25%) types.
• Other types include gastrointestinal stromal tumours (GIST) and secondary tumours.
• Clinical presentation often includes dysphagia, especially for solids, along with diagnostic methods like endoscopy and biopsy.

Squamous Cell Carcinoma (SCC)

• Most common in the mid third of the oesophagus.
• Histology shows keratinizing or non-keratinizing squamous lesions.
• Symptoms include dysphagia, odynophagia, and weight loss.
• Risk factors consist of dietary deficiencies, alcohol, tobacco use, chronic oesophagitis, achalasia, Plummer-Vinson syndrome, and genetic predispositions.

Adenocarcinoma

• Accounts for 85-90% of cases arising from Barrett's oesophagus, primarily located in the lower third of the oesophagus.
• Represents approximately half of all oesophageal malignancies, with a typical onset in the mid-60s.

Prognosis of Oesophageal Cancer

• Spread occurs locally, to lymph nodes, and through the bloodstream.
• Prognosis varies by stage:
  • 5-year survival for local disease ~45%, nodal disease ~25%, and distant spread ~5%.
• Treatment options include neoadjuvant chemotherapy and radiotherapy, oesophageal resection (40% success), stenting, and adjuvant chemotherapy/radiotherapy.

Inflammatory Disorders of the Stomach: Acute Gastritis

• Causes include alcohol, NSAIDs, steroids, smoking, corrosives, stress, uraemia, and gastric irradiation.
• Presentation may be asymptomatic or include epigastric pain, nausea, vomiting, anaemia, and gastrointestinal bleeding.
• Histologically shows neutrophilic influx and oedema.

Chronic Gastritis

• Associated chronic mucosal changes lead to mucosal atrophy and epithelial metaplasia.
• Most prevalent types:
  • Helicobacter-associated gastritis
  • Autoimmune chronic gastritis
  • Chemical/reflux gastritis
• Histology reveals lymphocyte and plasma cell infiltration.

Helicobacter-associated Gastritis

• Affects individuals at any age and primarily involves the antrum and corpus of the stomach.
• Caused by H. pylori, leading to epithelial damage, inflammation, and lymphoid aggregates.
• Increased risk for peptic ulcers and gastric cancer.

Autoimmune Chronic Gastritis

• Typically affects the elderly with autoantibodies against parietal cells.

• Associated with pernicious anaemia and increased gastric carcinoma risk (2-4%).Pernicious Anemia: It is a specific type of megaloblastic anemia caused by a vitamin B12 deficiency.

• There is a decrease in gastric acid production due to the loss of parietal cells, a condition known as hypochlorhydria.

  • Autoimmune chronic gastritis is often seen in conjunction with other autoimmune diseases, including:

    -Hashimoto’s thyroiditis (an autoimmune thyroid disorder).

    -Addison's disease (an autoimmune condition affecting the adrenal glands).

• Histological features include gland destruction and mucosal atrophy.

Chemical / Reflux Gastritis

• Results from the reflux of duodenal fluid and bile.
• Frequently occurs post-gastric surgery.
• Microscopy shows foveolar hyperplasia and fibromuscular changes.

intestinal metaplasia

• Associated with Chronic Gastritis
• refers to the transformation of gastric epithelium (the normal lining of the stomach) into intestinal-type epithelium. This means that the cells lining the stomach take on characteristics of those normally found in the small intestine.
• can progress to dysplasia
• Endoscopic Surveillance: Patients with intestinal metaplasia, especially those with chronic gastritis or a history of H. pylori infection, may require regular endoscopic surveillance.

Peptic Ulcer Disease

• Caused by gastric acid affecting various sites, including the duodenum and stomach.

• Represents a breach extending into the submucosa or deeper.

• Risk factors include H. pylori infection, blood group A, family history, and Zollinger-Ellison syndrome.

• Peptic ulcers: round-oval, sharply punched-out, straight walls, level margins, smooth base.

• Surrounding mucosa appears oedematous and reddened.

• Peptic ulcers – microscopic appearance

  • Ulcer on microscob shows fibrosis in the base and walls; has three zones: superficial slough, chronically inflamed granulation tissue, deep fibrous scar.
  • Vessel walls in scarred area may be thickened and occasionally thrombosed.

  clinical presentation for gastric and duodenal ulcers:

  Gastric Ulcers:

  • Pain: Epigastric pain that tends to be worse at night or 1-3 hours after eating.
  • Symptoms: Loss of appetite, weight loss, nausea, vomiting, bloating, belching.
  • Pain Characteristics: Often constant, can be aggravated by food.

  Duodenal Ulcers:

  • Pain: Typically relieved by eating or antacids. Pain may refer to the back, chest, or left upper quadrant (LUQ).
  • Symptoms: Iron-deficiency anemia, hematemesis (vomiting blood), melena (black tarry stools).
  • Complications: Penetrating ulcers can cause severe pain and potential perforation.

  Acute Gastric Ulcers (“Stress Ulcers”):

  • Development: Arise from acute erosive gastritis due to severe stress or shock (e.g., Cushing’s, Curling’s ulcers from burns or trauma) and can be drug-induced.
  • Microscopy: Ranges from erosion to ulceration, usually <1mm in size, single or multiple, without scarring or thickening of blood vessels.
  • Outcomes:
    • Severe bleeding.
    • Typically heal without scarring within days to several weeks.
    • May progress to chronic peptic ulcers.
  • Key Determinant: The ability to correct the underlying condition significantly affects the outcome.

Benign Tumours of the Stomach:

• Polyp: A nodule or mass projecting above the mucosa, uncommon in the stomach.
  • Hyperplastic Polyps (90%): Arise in chronic gastritis.
  • Adenomas (5-10%): Dysplastic epithelium with malignant potential, can be sessile or pedunculated.
  • Hamartomas: Includes Peutz-Jeghers and juvenile polyps.
  • Fundic Gland Polyps.
  • Lipomas.
  • Schwannomas.

Malignant Tumours of the Stomach:

• Carcinoma: Most common (90-95%).
• Lymphoma: 4%.
• Carcinoid Tumours: 3%.
• Mesenchymal Tumours: 2%, including:
  • GIST (Gastrointestinal Stromal Tumours): Range from benign to malignant.
  • Leiomyosarcoma.

Gastric Carcinoma:

• Histologically classified into intestinal and diffuse types.

• Epidemiology: Common cause of cancer-related deaths (after lung and colon), with a male-to-female ratio of 2:1. More prevalent in East Asia (Japan, China).

• Risk Factors:

  • Dietary: Smoked & salted foods, low fruit and vegetables, nitrites (from food, water, meat preservation).
  • Medical Conditions: Adenomatous polyps, pernicious anemia, prior partial gastrectomy, peptic ulcer disease.
  • Infection: H. pylori.
  • Metaplasia: Intestinal metaplasia.
  • Genetic: Blood group A, family history.

Spread occurs locally, via lymphatics (with involvement of Virchow’s node), or haematogenously.

gastric Carcinoma Locations and Prevalence:

• Antrum: 50-60% (most common site).
• Body: 30-40%.
• Fundus: 5-10% (least common).
• Cardia: 10-20% (associated with Barrett’s esophagus and GERD).

Gastric Cancer Spread and Prognosis:

• Spread:

  • Local: Adjacent organs like duodenum, pancreas, retroperitoneum.
  • Trans-coelomic: Krukenberg tumour in ovaries.
  • Lymphatic: Virchow’s node (supraclavicular) and Troisier’s sign.
  • Haematogenous: Bloodborne spread.

• Prognosis:

  • Localized: 70% 5-year survival.
  • Regional: 30% 5-year survival.
  • Distal (distant metastases): 5% 5-year survival.
  • Overall 5-year survival rate: 32%.

Early Gastric Cancer

• Confined to mucosa or submucosa, regardless of lymph node status.
• Cure rates are high for intramucosal (93%) and submucosal cancers (80-89%).

Gastrointestinal Stromal Tumours (mesenchymal tumor)

• Non-epithelial neoplasms arising from interstitial cells of Cajal. (“pacemakers” of the intestine)

• Often associated with CD117 (c-kit) mutations; treated with tyrosine kinase inhibitors like Gleevec™.

• Clinical features include:

   Adults

   Abdominal pain

   Melaena

   Rarely obstruction

Tumours of the Mouth

• Benign tumours include squamous papillomas linked to HPV types 6 & 11.
• Malignant cases are primarily squamous cell carcinomas, often found in the floor of mouth, tongue, and hard palate, with significant risk factors including tobacco and HPV 16/18.

Other Oral Conditions

• Aphthous ulcers may be associated with Crohn’s disease.
• Xerostomia (dry mouth) can be caused by autoimmune conditions or medications.
• Glossitis linked to nutritional deficiencies notably in vitamin B12 and iron or plummer-vinsion syndrom
• Leucoplakia (white plaque) poses a premalignant risk; hairy leukoplakia is HIV-associated with EBV infaection
• Erythroplakia has a high correlation with oral cancers, especially among smokers.

Salivary Glands Pathology

• Sialadenitis presents with sialorrhoea (excess saliva) and xerostomia.
• Benign tumours include pleomorphic adenomas (most common in parotid gland) and Warthin’s tumour.
• Malignant tumours are more frequently found in minor glands, often presenting with rapid growth and pain. Types include mucoepidermoid and adenoid cystic carcinoma.

Tumours of the Mouth

• Benign lesions include squamous papillomas associated with HPV types 6 and 11.
• Malignant tumours are primarily squamous cell carcinoma (>95%), linked to tobacco, alcohol, HPV types 16 and 18, and environmental factors.

Other Oral Conditions

• Aphthous Ulcers: May be related to Crohn’s disease.
• Xerostomia: Dry mouth resulting from autoimmune conditions, medications, or radiation.
• Glossitis: Deficiencies in B12 and iron; associated with Plummer-Vinson syndrome.
• Leucoplakia: White plaque not removable by scraping; cause unclear.
• Erythroplakia: Red, velvety patch with a high risk of malignancy; common in smokers and males.

Salivary Glands:

• Secrete proteins and fluid, categorized as mucinous or mixed.
• Ducts lined by cuboidal epithelium.

Pathology of Salivary Glands:

• Inflammation (Sialadenitis):

  • Can lead to Sialorrhoea (excessive saliva) or Xerostomia (dry mouth).
  • Parotid gland involvement:
    • Viral (e.g., mumps).
    • Suppurative (e.g., Staphylococcus aureus).
    • Autoimmune (e.g., Sjogren’s syndrome).

• Tumours:

  • Can be either benign or malignant.

Benign Tumours

• Typically present as painless swelling.

• Pleomorphic Adenoma: Most common parotid tumour.

  • More frequent in females than males.
  • Encapsulated structure with epithelial elements embedded in mucoid and chondroid stroma.
  • Treated through wide excision; however, local recurrence is common.
  • Difficult to completely excise, with a 25% chance of nucleation.
  • Risk of malignant transformation occurs in approximately 2%.

• Warthin’s Tumour: Accounts for 10% of parotid tumours.

  • Predominantly found in older males, especially smokers.
  • Features include a double layer of epithelial cells in a dense lymphoid stroma, with oncocytes and secretory cells, possibly exhibiting squamous metaplasia.
  • Known as "adenolymphoma."
  • Multifocality and bilateral occurrence found in 10% of cases.

Malignant Tumours

• More frequently observed in minor salivary glands.
• Indications of malignancy include rapid growth and pain.
• Types of Malignant Tumours:
  • Mucoepidermoid Carcinoma: Composed of glandular and squamous cells.
  • Adenoid Cystic Carcinoma: Characterized by cribriform, solid, and tubular gland formations, often with perineural invasion.
  • Acinic Cell Carcinoma: Resembles normal acinar cells.
  • Carcinoma ex Pleomorphic Adenoma: Originates from benign pleomorphic adenomas, transforming into malignant forms.

This quiz covers key concepts in Upper GI Pathology for Year 2 students at RCSI. It focuses on normal anatomy and conditions affecting the mouth, esophagus, and stomach, including benign and malignant tumors. Understand the causes of salivary gland enlargement and other related topics to prepare for your pathology exams.