Gastrointestinal pathology 2018 lecture 4. Dr Heyam Awad FRCPath

Transcription

1 Gastrointestinal pathology 2018 lecture 4 Dr Heyam Awad FRCPath

2 Topics to be covered Peptic ulcer disease Hiatal hernia Gastric neoplasms

3 Peptic ulcer disease (PUD)= chronic gastric ulcer Causes H pylori NSAIDS In USA ulcer due to NSAIDS is commoner nowadays than those due to H pylori due to 1. decreased pylori infection and 2. increased aspirin use in the aging population ( as a protection of thrombosis)

4 epidemiology 10% of males and 4% of females develop peptic ulcer in their lifetime Sites: PUD can occur in any site exposed to gastric acids ; antrum and first part of duodenum are the most common sites. It can also occur in the esophagus as a complication of reflux Ectopic gastric mucosa ( normal gastric mucosa in an abnormal location = choristoma) can also be affected.

5 H pylori and PUD 70% of PUD occurs in people with H pylori 5-10% of those with H pylori develop ulcer/ due to host factors and variability in pylori strains

6 pathogenesis 1. Hyperacidity: essential for the development of PUD hyperacidity can be caused by: H pylori, parietal cell hyperplasia, or increased gastrin like in Zollinger Ellison syndrome (see next slide) 2. NSAIDS 3. Smoking 4. Hypercalcemia: increases gastrin 5. Psychologic stress can increase acid secretion

7 Sites of PUD.. Duodenal ulcers four times more than gastric ulcers

8 Zollinger Ellison syndrome Multiple gastric ulcers in the stomach, duodenum and even jejunum.. Due to uncontrolled gastrin secretion from a tumor ( gastrinoma) which results in massive acid secretion. Remember that gastrin stimulates acid secretion.

9 Z-E syndrome

10 morphology Duodenum: stomach 4:1 80% of cases solitary Base of ulcer is clean and smooth Complication: perforation.. This is a surgical emergency

11 Clinical features Epigastric pain occurring 1-3 hours after meals, is worse at night and relieved by food or alkali. Nausea and vomiting Hemorrhage and anemia may occur

12 Treatment of gastric ulcer In the past surgical treatment was common Nowadays, treating H pylori and decreasing gastric acidity made surgery unnecessary except in complicated cases ( hemorrhage and perforation)

13 Hiatal hernia = separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the resulting gap Can be congenital or acquired. Asymptomatic in 90% of adult cases Symptoms similar to GERD can occur

14 Hiatal hernia

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16 Gastric neoplasms Gastric polyps Gastric adenocarcinoma Lymphoma Carcinoid tumor Gastrointestinal stromal tumors

17 Polyps: protrusions with smooth surface

18 Gastric polyps / types Inflammatory and hyperplastic polyps Gastric adenoma

19 Hyperplastic and inflammatory polyps 75% of gastric polyps are inflammatory or hyperplastic Occur in people years Arise in the background of chronic gastritis that initiates the injury and reactive hyperplasia If associated with H pylori gastritis, polyps may regress after bacterial eradication Dysplasia can occur within hyperplastic polyps and risk increases with larger polyps : usually larger than 1.5 cm

20 Hyperplastic polyp: there is hyper plastic glands and no dysplasia

21 Gastric adenoma years of age Male: femal 3:1 Almost always occur in the backgrounfd of chronic gastritis with atrophy and intestinal metaplasia To call a polypoid lesion an adenoma, it must contain dysplasia. So: by definition, adenomas contain dysplastic glands. Risk of developing carcinoma is related to the size and is elevated in lesions more than 2 cm

22 Gastric adenoma.. Dysplasia is essential to diagnose adenoma

23 Gastric adenocarcinoma 90% of gastric tumors are adenocarcinomas More common in Japan Costa Rica and Eastern Europe Symptoms: nausea, vomiting and epigastric pain.. All are non specific which delays diagnosis

24 Epidemiology Gastric carcinoma is decreasing in the developed countries due to better control of H pylori and improved living conditions

25 pathogenesis Most important mutations: Loss of E cadherin B catenin mutation H pylori and EBV infection predisposes to gastric carcinoma

26 E cadherin mutation ( loss of E cadherin) causes decreased contact inhibition, which causes cancer.

27 Beta catenin mutation causes decreased contact inhibition and increased proliferation through stimulating transcription factors.

28 Lauren classification of gastric adenocarcinoma Adenocarcinoma is classified into two types: 1. Intestinal type: the tumour forms glands that look like intestinal glands. This type mostly occurs as a complication of chronic gastritis. 2. Signet ring type. here the tumour cells grow as individual cells with no gland formation.

29 Lauren classification of gastric adenocarcinoma: intestinal type ( pic a)and diffuse (signet ring type)( pic b and c)

30 Clinical features Intestinal type: occurs mainly in high risk areas: Japan, Costa Rica Develops from dysplasia or adenoma Mean age 55 Male : female= 2:1 Present as mass lesions

31 Diffuse type Incidence is uniform across countries No known pre-cancer lesion Male: female 1:1 Present as thickening of the stomach wall with no mass.

32 Gastric carcinoma/ mass.. Most likely intestinal type

33 Intestinal type: gland formation

34 Diffuse type.. Lenitis plastic/ note that the wall is thickened with no mass

35 Diffuse carcinoma: note that all the wall is thickened.

36 Signet ring cells in diffuse gastric carcinoma.. Nucleus pushed to one side (to the periphery) by the mucin secreted inside the cytoplasm.

37 Diffuse, signet ring carcinoma

38 Prognosis: depends on TNM stage

39 outcome 5 year survival for early lesions: 90% even if there is lymph node metastasis 5 year survival for advanced disease: 20% Overall 5 year survival 30%.. Because of late detection

40 lymphoma the most common type of gastric lymphoma is: MALTOMA = mucosa associated lymphoid tissue lymphoma It s an indolent ( low grade) lymphoma arising from the lymphocytes within the gastric mucosa Other types of lymphoma can arise in the stomach H pylori increase the risk of gastric MALTOMA.

41 Carcinoid tumor Neuroendocrine tumors arising from neuroendocrine cells like the G cells Can be associated with endocrine cell hyperplasia, chronic atrophic gastritis and Zollinger Ellison syndrome Symptoms depend on the hormone produced by the tumor cells Gastric and esophageal carcinoids have better prognosis than those in the jejunum

42 Gastrointestinal stromal tumor (GIST) Mesenchymal tumor of the stomach and other parts of the GI tract Peak at 60 years of age Males more than females Cell of origin/; interstitial cell of Cajal Majority have c-kit mutation C-kit is a tyrosine kinase people with this mutation benefit from targeted therapy= imatinab

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