Gastric carcinoma Dr.Ashraf Abdelfatah Deyab Assistant professor of Pathology Faculty of medicine- Majma’ah University

Gastric Carcinoma- Objectives ä Discuss its epidemiology & Impact. ä Explain the causes and risk factors. ä Describe the morphology & laboratory diagnosis. ä Discuss screening & prevention (Japan experience). ä (Robbins Basic Pathology, 8 th ed. P ).

Gastric adenocarcinoma ä Most common malignancy of stomach > 90% of all gastric tumor- ä 4 th commonly occurring cancer in the world. ä 2nd cancer related to the death. ä With Significant geographical distribution, Japan, Chile, italy,east europe > 20 fold of USA, north Europe, Africa, SE ASIA. Preventable??? ä Marked drop recently in USA+ Europe suggested control of Enviromental & Dietary factors. ä >> common in:(1) lower socioeconomic groups. ä 2) Multifocal mucosal atrophy& intestinal metaplasia.

Stomach- normal anatomy Cardia Fundus Antrum Pylorus Normal gastric fundus; note specialized Parietal Cell: oxyntic mucosa\pink. Chief cells)= purple beneath the top layer of mucus glands..

Etiology& Risk group ä Genetic factors: ( BLOOD group A, Family history, Familial hereditary syndrome) ä Host factors: ( chronic gastritis, intestinal metaplasia, partial Gastrectomy, gastric adenoma, dysplasia, reflux, Barrett's esophagus, Autoimmune gastritis –hypochlorhydra& PH change). ä Environmental factors: ( H.pylori infection, Diet “smoked food-fish-meat-salt, lack of fresh fruit and vegetable”= N-nitroso,, cigarette smoking)

Gastric carcinoma Pathogenesis ä The majority of gastric ca. pathogenesis is closely related to environmental factors (not genetic) ä interaction between host genetic background and environmental factors still play a major role ä multistep progression, from chronic gastritis to intestinal metaplasia, dysplasia, and carcinoma. ä 1) Genetic factors: molecular genetics of gastric cancer has been established: ä a) Allelic loss has been identified at a variety of loci on various chromosomes.

Gastric carcinoma Pathogenesis ä b) CDH gene mutations are identified in familial gastric cancer, (Encode E-cadherin)- lead to Diffuse type gastric ca ä CDH mutations are present in about 50% of sporadic cases of diffuse gastric tumors. ä c) P53 mutations are present in the majority of sporadic gastric cancers. ä d) FAP individual: associated with increased risk of intestinal-type

Gastric carcinoma Pathogenesis ä 2) Host & environmental factors: ä a) Gastric PH change >> promotes the growth of bacteria>> reduce dietary nitrate to nitrite then >>convert dietary amines, in the presence of this nitrite, into carcinogenic N-nitroso compounds. ä B) H.pylori infection through its role in the development of chronic gastritis ä b) Coexistence of chronic atrophic gastritis “controversial”

Gastric adenocarcinoma-morphology ä classified according to their location in the stomach: (Ant.\post. wall+ lesser, greater, curv.) ä The gastric antrum & lesser curvature are involved > >> often greater curvature. ä Histological Types divided into : ä 1) Intestinal type adenocarcinoma ä 2) Diffuse type gastric adenocarcinoma ä Note:” Early” gastric carcinoma variant described by Japanese

Chronic Atrophic Gastritis with intestinal metaplasia

Early’ gastric carcinoma : confined to mucosa, submucosa (not extending into muscularis ),

Intestinal type of gastric adenocarcinoma ä Different gross macroscopic appearance; 1)Exophytic (bulky, polypoidal). ä 2)Endophytic (invasive, ulcerative,excavated). ä Microscopic pattern: infiltrating neoplastic glands in varying degree of differentiation (tubular or papillary). ä a\w H.pylori chronic gastritis with intestinal metaplasia & atrophy “precursor” - ä Also a\w FAP individual patients “rare”.

Gastric adenocarcinoma-morphology macroscopic growth pattern

Gastric carcinoma- intestinal type

Diffuse type of gastric adenocarcinoma ä Rigid gastric wall. “Leather bag”= linitis plastica. ä Composed of diffuse sheet of dyscohesive signet ring cells. ä Background of variable amount of “pools” mucin lacks with Desmoplastic stroma. ä a\w CDH gene mutations- dyscohesive distrubtion.

Diffuse gastric carcinoma- linitis plastica Mucinous (mucoid)carcinoma

WHO classification of stomach carcinoma (Histologic variants) The diagnosis is based on the predominant histological pattern. Tubular adenocarcinomas Mucinous adenocarcinomas Papillary adenocarcinomas Signet-ring cell carcinomas Adeno-squamous carcinoma Squamous cell carcinoma Undifferentiated carcinoma

Grading of Gastric Adenocarcinoma G1, G2, G3 ä Adenocarcinoma may be graded into: ä Well-differentiated (> 95% of tumor composed of glands). ä Moderately differentiated ( 50% to 95% composed of glands). ä Poorly differentiated ( 49% or less composed of glands)

Gastric ca. clinical features ä Intestinal type (better prognosis >> intestinal type) ä The mean age of presentation is 55 years. - Male-to-female ratio is 2 : 1, arise from. - Considered as precursor: flat dyplasia & adenoma. - Closely associated with atrophic + metaplasia. ä Diffuse type: “poor prognosis” ä (Rarely in elderly, occasional in child). ä No identified precursors. ä With similar frequency between male and female. ä The depth of invasion and the extent of local nodal and distant metastasis at the time of diagnosis. ä

Gastric carcinoma- Clinical Findings ä Symptoms& Signs: ä If the tumor is located in the cardiac or pyloric areas, it may produce obstruction relatively early ä Otherwise “non-specific”; weight loss, dyspepsia, abdominal pain, anorexia, vomiting\ Pyloric obstruction, altered bowel habits, dysphagia, anemia, and hemorrhage.- mimic chronic gastritis. ä These tumors are often discovered at advanced stages, +\- left supra-clavicular region Virchow node.

Gastric ca. clinical features ä Metastasize to ( trans-coelmic, lymphatic, haematogenous ) ä - Supra-clavicular sentinel lymph node= Virchow's node ä - Peri-umbilical region to form subcutaneous nodule, termed a Sister Mary Joseph nodule. ä Ovarian involvement generates Krukenberg tumors ä Local invasion duodenum, pancreas, and retroperitoneum. ä Management: Surgical resection with chemotherapy or radiation therapy + or palliative management in advanced cases.

Spread of gastric carcinoma (Virchow node)

Spread of gastric carcinoma ä Lymphatic spread: mucosal or sub-mucosal plan- (greater& lesser curvature LN, para- aortic, supra-clavicular” virchow sign” ) ä Hematogenous spread: liver, lung. ä Trans-coelomic – both ovaries. ä Direct spread to adjacent structure- ä Metastatic tumors to the stomach are relatively uncommon

Screening & prevention (Japan experience). ä Gastric ca. is leading cause of death –Japan, 1983 ä Japan MOH: set National guidelines, adopted a successful Mass screening program “nationwide for the resident” for early detection and prevention, 35% - are early gastric cancer. ä Screening tools : Barium studies, Upper GI endoscopy. Serum pepsinogen tests- for atrophic gastritis Dx. + screening for H. pylori Antibodies Others preventive measures

Screening & prevention (Japan experience). ä Target group: Screening for > 40 years, also some specific patients. ä Duration ; every 2 year. ä Unfortunately, mass screening programs are not cost-effective in low incidence area – USA

Prevention overall reduction in gastric cancer incidence is unknown?? how to modify the Risk factors ä 1) Decreased consumption of dietary carcinogens, ( e.g N-nitroso compounds ). ä 2) Reduced use of salt and smoked food. ä 3) Increase intake of green, fresh leafy vegetables and citrus fruits, which contain antioxidants such as vitamin C, vitamin E, and beta-carotene. ä 4) Improved food transportation networks. 5)Widespread availability of food refrigeration for food preservation..

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