Epstein-Barr virus (EBV). While H. pylori is most commonly associated with gastric cancer, approximately 10% of gastric adenocarcinomas are associated with Epstein-Barr virus (EBV) infection. Although the precise role of EBV in the development of gastric adenocarcinomas remains to be defined, it is notable that EBV episomes in these tumors frequently are clonal, suggesting that infection preceded neoplastic transformation. Further, TP53 mutations are uncommon in EBV-positive gastric tumors, suggesting that the molecular pathogenesis of these cancers is distinct from that of other gastric adenocarcinomas. Morphologically, EBV-positive tumors tend to occur in the proximal stomach and most commonly have a diffuse morphology with a marked lymphocytic infiltrate.
MORPHOLOGYGastricadenocarcinomasareclassifiedaccordingtotheirlocationinthestomachaswellasgrossandhistologicmorphology.TheLauren classification thatseparatesgastriccancersintointestinal anddiffuse typescorrelateswithdistinctpatternsofmolecularalterations,asdiscussedearlier.Intestinal-typecancerstendtobebulky(
Fig.15.16A )andarecomposedofglandularstructuressimilartoesophagealandcolonicadenocarcinoma.Intestinal-typeadenocarcinomastypicallygrowalongbroadcohesivefrontstoformeitheranexophyticmassoranulceratedtumor.Theneoplasticcellsoftencontainapicalmucinvacuoles,andabundantmucinmaybepresentinglandlumina.
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Fig.15.16B )andarecomposedofdiscohesivecellswithlargemucinvacuolesthatexpandthecytoplasmandpushthenucleustotheperiphery,creatingasignet ring cell morphology(
Fig.15.16C ).Thesecellspermeatethemucosaandstomachwallindividuallyorinsmallclusters.Amassmaybedifficulttoappreciateindiffusegastriccancer,buttheseinfiltrativetumorsoftenevokeadesmoplastic reactionthatstiffensthegastricwallandmaycausediffuserugalflatteningandarigid,thickenedwallthatimpartsa“leatherbottle”appearancetermedlinitis plastica.
Intestinal-type gastric cancer predominates in high-risk areas and develops from precursor lesions such as dysplasia and adenomas. The mean age at presentation is 55 years, and the male-to-female ratio is 2:1. By contrast, the
Fig. 15.16 Gastricadenocarcinoma.(A)Intestinal-typeadenocarcinomaconsistingofanelevatedmasswithheaped-upbordersandcentralulceration.Comparewiththepepticulcerin
Fig.15.15A . (B)Linitisplastica.Thegastricwallismarkedlythickened,andrugalfoldsarepartiallylost.(C)Signetringcellswithlargecytoplasmicmucinvacuolesandperipherallydisplaced,crescent-shapednuclei.
incidence of diffuse gastric cancer is relatively uniform across countries, there are no identified precursor lesions, and the disease occurs at similar frequencies in males and females. Of note, the decrease in gastric cancer incidence applies only to the intestinal type, which is most closely associated with atrophic gastritis and intestinal metaplasia. As a result, the incidences of intestinal and diffuse types of gastric cancers are now similar in some regions.