hello everyone welcome to this short tutorial from pathology Made Simple at ILO pathology.com now in continuation with the uh series on gastrointestinal system pathology for undergraduates so today let's discuss about carcinoma stomach and in particular we will see the differences between the intestinal type versus diffuse type of carcinoma stomach so the learning objectives will be we will just look into the idiopathogensis of gastric cancer and then just enumerate the differences between intestinal type and the diffuse type of gastric cancer now among the various gastric cancers gastric adenocarcinoma is the most common malignancy of the stomach which comprises more than 90 percent of all gastric cancers so when we look into the epidemiological aspects of gastric cancers in countries like Japan Chile you know Costa Rica Eastern Europe the incidence is up to 20 fold higher than in countries like North America northern Europe Africa and Southeast Asia what is important to note that the gastric carcinoma is more common in the lower socioeconomic groups as well as in individuals with multifocal mucosal atrophy and intestinal metaplasia now look what are the what are all the risk factors for the development of gastric adenocarcinoma now one by one let's understand these various risk factors gender committee to the gender males are more commonly affected and it's most often seen in sixth to eighth decade of life and it is all most always associated with helicobacter pylori particularly there is such pylori which you know has this CAG strain c-a-g-a strain that is cytotoxin associated Gene a protein okay so we know that this particular strain this particular protein is both pro-inflammatory as well as proproliferative this we have discussed in Greater detail when I explained when I talk to you about H pylori Associated gastritis you can go back to that video and then look into this so coming to the dietary factors the diet which are rich in nitrogamines particularly the smoked fish and meat these are the individuals who are at risk for developing adenocarcinoma smoking and tobacco is another independent risk factor for development of adenocarcinoma so all these factors combined together forms the environmental factors or environmental risk factors for the development of adenocarcinoma now if the patient have had previous gastric surgery you know they are also at risk for development of carcinoma because the previous gastric surgery results in decreased acid secretion and subsequent proliferation of nitrite producing bacteria which is carcinogenic patients with pernicious anemia you know patients with Miniatures disease are hypertrophic gastropathy and other predisposing diseases like autoimmune gastritis atrophic gastritis gastric ulcer and even gastric dysplasia are all these are risk factors for development of gastric carcinoma and these all combined together forms host factors a third important category of risk factors are patients with blood group a they are found to be associated with most often associated with gastric Cancers and syndromes like you know know hereditary non-poliposis colon cancer and familial adenomatosis polyposis so these are the two important syndromes which are associated with increased risk of developing gastric Cardinal carcinoma and of course lastly the mutations involving various genes we shall discuss about these mutations a bit later so all these constitutes genetic factors so the risk factors can be well you know understood by these three categories environmental factors host factors and genetic factors of late you know the overall incidence of gastric adenocarcinoma is decreasing the possible reasons for that is one reduced rates of helicobacter pylori infection and two decreased consumption of dietary carcinogen such as you know nitroso compounds and benzo pyrene and that's because of reduced use of salt and smoking for food preservation and the widespread availability of refrigeration okay now how do you classify gastric cancers So based on the depth of invasion based on the macro scopic growth pattern and based on the microscopic types based on the depth of invasion they classified as early and advanced cancer where early gastric cancer meaning you know the invasive carcinoma is confined to mucosa and are sublucosa they go they don't go beyond mucosa and submucosa it can be with or without lymph node metastasis irrespective of tumor cells what is important this confinement within the mucous and submucosa whereas Advanced gastric cancers are the ones which invade into the muscularis propria and Beyond based on the macroscopic growth patterns the gastric cancers are classified into the flat type the exophytic type the ulcerated type and diffuse type now based on the histological picture they are categorized into intestinal and diffuse this is age-old classification based on this Landmark paper by Lauren that's why this is called as Lawrence classification of gastric cancers into intestinal and diffuse type of cancers now let us understand the pathogenesis of these two types of cancer separately so now we will try to differentiate between intestinal and diffuse type of gastric cancers the pathogenesis for intestinal type of gastric cancer is basically due to increased signaling via the wnt pathway when I explained you about the carcinoma colon we have talked about wnt pathway right that's very important for the proliferation of the cells and two important proteins are involved one is APC another is beta catanin so what really happens here is if there is a mutation involving the APC Gene the APC is a tumor suppressor Gene the mutations can be of loss of function mutations in the adenomatous polyposis coli gene or it can be gain of function mutations in the gene encoding beta-catinine so whatever the what whatever the reason whether it is loss of function mutation of this or gain of function mutation of beta-catinine ultimately it results in increased signaling via the wnt pathway thereby you know resulting in uninhibited proliferation see the other mutations involved are genes in involved in TGF signaling genes involved in regulation of apoptosis like baxtin and genes involved in cell cycle control like c d k and 2A genes so the mutations of these genes are involved or implicated in the development of intestinal type of gastric cancer now coming to the diffuse type of gastric cancer the most important mechanism is the loss of e-catherine we know that e Catherine is basically the one which helps the cells to attach to one another okay so that they they are basically transmembrane protein so loss of this e Gathering results in dissociation of cells now why is that there is either in loss that's because of loss of function mutations in tumor suppressor Gene called cdh1 because this cdh1 is the one which encodes each other in so other reasons for each other in loss is hyper methylation and silencing of the cdh1 promoter region so whatever the cause the equator in loss is the one which results in diffuse type of gastric cancer so once we have understood this pathogenesis we should realize that sporadic gastric cancers are almost always of intestinal type whereas familial gastric cancels usually they are of diffuse type of gastric cancer now coming to the morphology of gastric cancers how does intestinal type look they are often bulky tumors as compared to that of diffuse type of gastric cancer these tumors it is intestinal type of tumors they frequently grow along broad cohesive front to form either an exophytic mass or an ulcerated infiltrative tumor like this so it can be a polypoid mass it can be an ulcerated tumor or it can be fungating proliferated fungating growth so these are the various morphological patterns of diffuse I mean intestinal type of gastric cancers which are basically bulky tumors now in contrast the diffuse types are often infiltrated tumors and because of these infiltration they evoke desmoplastic response and that stiffens the gastric wall okay and once the gastric wall is stiffened you know there is large areas of infiltration diffuse rugel flattening and rigid thickened wall which looks like The Duffer leather bottle and that's why it is referred to as linitis plastic or leather bottle stomach this is a very classical morphology of diffuse type of gastric cancer now coming to the microscopic picture the intestinal type of gastric cancer they are composed of glandular structures okay and the cells of these glandular structures they often contain apical mucine vacuoles and you can see abundant mucin within the gland Lumina as well whereas diffuse type you know they are composed of Signet ring cells now what do you mean by signaturing cells Signet basically means a seal in the earlier days you know there used to be ring along with the ceiling the front of that particular thing and that's where they were referred to as signaturing basically used for um you know playing seal so this is a signaturing cell and these are basically cells which have very large mucine vacuoles that expand the heteroplasm thereby pushing the nucleus to the periphery which looks like that of a signaturing morphology that's where they are referred to as signaturing cells so this is a classical histological picture of signaturing cell carcinoma which is a diffuse type of gastric cancer now can we make a difference or is there any difference between the clinical features of both these cancers uh predominantly the manifestations are similar if you're looking at early symptoms you know they resemble just like that of a chronic gastritis and peptical Ulcer Disease like you know they have dyspepsia they have dysphagia and even nausea most often these symptoms are neglected and that's why majority of the patients of gastric cancer they're present are often discovered at Advanced stages where they manifest with weight loss anorexia early satiety that is particularly in primary in diffuse cancers anemia and even Hemorrhage so those were the you know Common manifestations but there are some differences in both these cancers intestinal as well as diffuse intestinal cancers they are predominantly found in high risk areas what we saw earlier in epidemiological pattern right diffuse cancers they are relatively uniform across the countries intestinal type you know they are often they often have precursor lesions including dysplasias and adrenal no such lesions no such identified precursor lesions for diffuse type of cancers the main age of presentation is around 55 years usually elderly individuals and the male to female ratio is two is to one males are more commonly affected whereas diffuse type of cancers you know they are often seen in younger people and then the prevalence is similar in both males and females intestinal type of cancer is H pylori Associated whereas no such Association or no role of H pylori in diffuse type of cancer and dietary factor is also important in the pathogenesis of intestinal type of cancer whereas no such role for diffuse type of cancers okay so if you remember I have told you this statement right of late the incidence of gastric Cardinal carcinoma is decreasing and this is applicable only for the intestinal type of gastric cancer and not for the diffuse type of gastric cancer you know what are all the prognostic indicators what is the most powerful prognostic indicator they are the depth of invasion and the extent of nodal and distant metastasis these are the two important prognostic indicators for gastric carcinoma so usually metastasis are found in advanced gastric cancers now where all we can find metastasis one it can be in this of course Regional lymph nodes are there but then distant metastasis includes they can be supraclavicular Sentinel lymph nodes they are known as War cow node and they can be seen around the umbilicals they are peri-ambolical lymph nodes they are referred to as Sister Mary Joseph nodules they can be you know metastasized to ovaries but this happens particularly in diffuse type of cancers particularly significant cell carcinoma and these are known as krukenberg tumor which are actually bilateral metastatic deposits from gastric signaturing cell carcinoma and lastly they can message exercise to the left axillary lymph node and even the pouch of Douglas and coming to the treatment of gastric cancer whenever possible wherever possible surgery Remains the preferred treatment approach but in advanced cases chemotherapy or radiation therapy and palliative care and when we look into five year survival rate of gastric cancers early gastric cancers particularly which are amenable to surgical resection The Five-Year survival is more than 90 percent whereas in advanced cases it drops down to less than 30 percent so that's about the etiopathogenesis of gastric cancer and then we did try to enumerate the differences between intestinal and diffuse type of gastric cancer thank you for watching 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