Robbins Essential Pathology_p257-262.pdf

CHAPTER 12 Gastrointestinal System 207 Esophageal Tumors...

CHAPTER 12 Gastrointestinal System 207 Esophageal Tumors he overa 5-year sur vva rae s 9%, wc ncreases o 75% n he wo major ypes o esopagea cancer are adenocarcnoma and paens w superca carcnomas. squamous ce carcnoma. Squamous ce carcnoma s more common n Asa. Is ncdence n e Uned Saes s decreasng, bu e nc- dence o adenocarcnoma s gong up. DISORDERS OF THE STOMACH    Adenocarcnoma usuay arses n regons o Barre esopagus n Gastritis and Peptic Ulcer Disease paens w ong-sandng GERD. Progresson rom e dyspasa Gastritis is inammation of the gastric mucosa resulting from o Barre esopagus o carcnoma nvoves sequena acquson exposure to acid and other injurious agents, and is usually due o genec and epgenec canges. TP53 muaons and cromo- to an imbalance between damaging factors and mechanisms that soma copy number canges are oten seen. he umors are mos protect the stomach lining from these agents. oten ocaed n e dsa esopagus; eary esons appear as la or Gasrs may be acue or cronc. rased paces n oer wse nac mucosa, wereas aer umors may orm arge exopyc masses assocaed w dyspaga (Suppemen- Acute Gastritis a eFg. 12.5). On mcroscopc examnaon, umors ypcay pro- Acue gasrs may be asympomac or  may cause epgasrc pan, nau- duce mucn and orm gands. Paens presen w pan, dicuy sea, and vomng. In more severe cases, ere may be uceraon and em- n swaowng, vomng, and weg oss. By e me sgns and orrage, resung n emaemess (vomng o bood) and bood oss. sympoms appear, e umor usuay as nvaded e submucosa ympac vesses; due o e advanced sage a dagnoss, e overa Pathogeness. he gasrc umen s srongy acdc, w a pH cose o 5-year sur vva rae s ess an 25%. 1—more an 1 mon mes more acdc an e bood. I aso con-    S quamous ce carcnoma s assocaed prmary w acoo and ans proeases and oer enzymes. hs ars envronmen conrbues obacco use (wc synergze o ncrease rsk), as we as causc o dgeson o ood bu aso as e poena o damage e mucosa. esopagea njur y, acaasa, Pummer-Vnson syndrome (ron Mupe mecansms ave evoved o proec e gasrc mucosa (Fg. decency anema, dyspaga, and esopagea webs), requen con- 12.2). Mucn secreed by surace epea ces orms a n ayer o sumpon o ver y o beverages, and prevous radaon erapy o mucus a seds e mucosa;  as a neura pH as a resu o secre- e medasnum. I s more common n peope o Arcan descen on o bcarbonae ons by epea ces. he rc bood suppy o an n Caucasans, a dference no accouned or by known rsk e gasrc mucosa eiceny bufers and removes proons a dfuse acors. Unke adenocarcnoma, ese umors are ocaed n e back no e amna propra. Gasrs can occur ater dsrupon o upper or mdde rd o e esopagus and nay appear as any o ese proecve mecansms or augmenaon o njurous expo- sma, gray-we, paque-ke ckenngs a can evove no po- sures. he man causes o cemca gasrs ncude e oowng: ypod umor masses a prorude no and obsruc e umen,    Nonsteroda antnammatory drugs (NSAIDs) nb producon or no uceraed, dfusey nrave esons (see Suppemena o prosagandns, wc normay smuae mucn and bcarbonae eFg. 12.6). Hsoogcay, mos are we o moderaey dferenaed. NORMAL INJURY ULCER Damaging Forces: H. pylori infection Gastric acidity NSAID Peptic enzymes Aspirin Tobacco Alcohol Gastric hyperacidity Duodenal-gastric Mucus reflux Mucosa Defensive INJURIOUS EXPOSURES Forces: Necrotic OR debris Surface mucous IMPAIRED DEFENSES Muscularis secretion mucosae Bicarbonate Acute secretion into mucus inflammatory Mucosal blood flow cells Apical surface Granulation Ischemia membrane transport Submucosa tissue Shock Epithelial regenerative Delayed gastric capacity emptying Fibrosis Prostaglandin Host factors synthesis Fig. 12.2 Mechanisms of gastric injury and protection. This diagram illustrates the progression from mild forms of injury to ulceration that may occur with acute or chronic gastritis. Ulcers include layers of necrotic debris, inflammation, and granulation tissue; scarring, which develops over time, is present only in chronic lesions. NSAID, nonsteroidal antiinflammatory drug.  CHAPTER 12 Gastrointestinal System 207.e1 A B Supplemental eFig. 12.5 Esophageal adenocarcinoma. (A) The tumor usually occurs distally and, as in this case, often involves the gastric cardia. (B) Esophageal adenocarcinoma organized into back-to-back glands. A B Supplemental eFig. 12.6 Esophageal squamous cell carcinoma. (A) The tumor is most frequently found in the midesophagus, where it commonly causes strictures. (B) Squamous cell carcinoma composed of nests of malignant cells that partially recapitulate the organization of squamous epithelium. 208 CHAPTER 12 Gastrointestinal System H. pyor necon s aso assocaed w an ncreased rsk o gasrc secreon and mucosa bood low. Ingeson o ese drugs s a re- carcnoma and ympoma (dscussed aer). quen cause o gasrc mucosa njur y.    Urema and nfecton by Hecobacter pyor (dscussed aer) may nb gasrc bcarbonae ransporers. Morphology. Bacera are presen n e mucus overyng epea    C  e m c a e x p o sure s , esp e c a  y o acds and a  ka s, a coo, ces (Fg. 12.3), parcuary oveoar ces n e anrum; ncreased and c  e m o  e r ap e u  c dr ugs, m ay d  re c   y  nj u re  e gas r c acd producon and gasrs ypcay occur n e anra regon. mu c o s a. Inesna meapasa, caracerzed by e presence o gobe ces and Acue gasrs s caracerzed by e presence o neurops wn coumnar absorpve ces, may be presen. Varabe numbers o neu- e epea ayer ; n severe cases, ere s eroson o e mucosa ead- rops are seen n e amna propra, epeum, and gasrc ps. ng o emorrage, wc may be e reaenng. he amna propra aso conans ympocyes and macropages, as s ypca o cronc nlammaon, and sees o pasma ces. he mucosa may conan ympod oces w germna ceners. Stress-Related Gastritis Paens w severe rauma, burns, exensve surger y, and crca nesses are prone o deveopng acue gasrs n e orm o sress Clncal Features. Paens presen w ypca sgns o gasrs, suc ucers: as epgasrc pan, nausea, and vomng. he bacera may be dened    Curng ucers occur n e proxma duodenum and are assocaed n gasrc bopses usng mmunosocemca sans and by cuure. w severe burns or rauma. Ureases produced by e bacera break down urea no ammona,    Cusng ucers arse n e somac, duodenum, or esopagus o ose wc can be deeced by brea ess. A soo es or e presence o w nracrana dsease and ave a g ncdence o peroraon. H. pyor angen s used or e dagnoss o acve dsease. Anbocs can eradcae H. pyor and aow resouon o gasrs. In unreaed Pathogeness. Sress-reaed mucosa njur y may sem rom oca sc- cases, e proonged mmune response n e mucosa-assocaed ema due o sysemc ypoenson or reduced bood low caused by ympod ssue (MALT) can resu n e deveopmen o ow-grade vasoconsrcon (rggered by sympaec ner vous or oer neura exranoda margna zone ympomas (aso caed MALTomas). Ines- mpuses), as we as ncreased acd producon secondar y o smua- na meapasa s a rsk acor or e deveopmen o gasrc carcnoma. on o e vagus ner ve. Sysemc acdoss may exacerbae e damage by owerng e nraceuar pH o mucosa ces. Morphology. he mucosa sows saow erosons or acue ucers, oten mupe. Unke cronc pepc ucers, ere s no scarrng o e ucer bed or ckenng o e bood vesse wa. C ln cal Feature s. Mos cr  c a  y  p a  ens ad me d o  ne ns ve c are uns sow s ome e v  d ence o g as r  s , w  c may e ad o s e ve re be e dng and e ven p er ora  ons. Tre a men o  e und e ry  ng c on- d on usu a  y resu s n res ou  on o  e  n   am ma on and re p a r o  e ep eum. Helicobacter pylori Gastritis A B Infection with the H. pylori bacillus causes chronic gastritis and duodenal and gastric ulcers. Pathogeness. H. pyor s a spra-saped bacus deecabe n gasrc mucosa bopses rom e majory o paens w duodena ucer and cronc gasrs, aoug e ncdence s decreasng n ger- ncome counres. Inecon raes are nversey correaed w paen age, and e necon s oten acqured durng cdood, especay n areas w crowded vng condons and poor sanaon. he bacera nvade e gasrc mucosa and, wou erapy, generay perss or e. As a resu o mproved sanaon, e ncdence o H. pyor nec- on n cdren as aen. he bacera are oug o cause gasrc epea njur y by severa mecansms, ncudng e oowng:    Reease o bactera enzymes and oer oxc producs a drecy C D damage epea ces Fig. 12.3 Chronic H. pylori gastritis. (A) Spiral-shaped H. pylori bacilli are    Increased producon o gastrc acd, n par by smuang gasrn highlighted in this Warthin-Starry silver stain. Organisms are abundant secreon and n par by reducng e producon o pysoogc within surface mucus. (B) Intraepithelial and lamina propria neutrophils are nbors o acd secreon prominent. (C) Lymphoid aggregates with germinal centers and abundant    Producon o proteases a degrade normay proecve gycopro- subepithelial plasma cells within the superficial lamina propria are char- ens n e mucous ayer, exposng epea ces o e ars gas- acteristic of H. pylori gastritis. (D) Intestinal metaplasia, recognizable as rc conens the presence of goblet cells admixed with gastric foveolar epithelium, can    Smuaon o acue and cronc nammaton and cyokne reease develop and is a risk factor for development of gastric adenocarcinoma.  CHAPTER 12 Gastrointestinal System 209 Autoimmune Gastritis Gastric Polyps and Adenomas Auommune gasrs as dverse consequences, ncudng an ncreased Gasrc poyps may be nlammaor y or neopasc, wereas adenomas rsk o gasrc cancer and deveopmen o vamn B decency. are neopasms a may ser ve as precursors or cancers. 12    Poyps are nodues or masses projecng rom e mucosa. hey Pathogeness. This form of gastritis is caused by an autoimmune are requen ncdena ndngs n endoscopes. he majory are attack on gastric parietal cells. nlammaor y or yperpasc, arsng n areas o reacve yperpa- Bo auoreacve T ces and auoanbodes agans parea epea sa caused by cronc gasrs (Suppemena eFg. 12.8A,B). In e ces and nrnsc acor ave been mpcaed n e paogeness; wc s gasrc body and undus, poyps are oten mupe bu usuay o - more mporan n causng parea ce damage s unceran, bu deecon e consequence. Proon pump nbors used or e reamen o o e anbodes s dagnoscay epu. Parea ce oss eads o decreased gasrc acdy may gve rse o undc gand poyps because reduced producon o gasrc acd (acorydra) and nrnsc acor. Acorydra acdy ncreases gasrn secreon, wc n urn causes gandu- can aow bacera overgrow and secondary yperpasa o gasrn-pro- ar yperpasa. In Wesern counres, because e prevaence o ducng eneroendocrne ces. Loss o nrnsc acor reduces absorpon H. pyor necon s ow and e use o proon pump nbors s o vamn B and can ead o perncous anema, wc s reversbe (see common, undc gand poyps are e mos requen ype o poyp. 12 Caper 9). More omnous s rreversbe neuroogc damage.    Adenomas represen abou 10% o gasrc poyps; e ncdence ncreases w age, and mos paens are beween 50 and 60 years o age. Maes are afeced ree mes more oten an emaes. Adeno- Morphology. he acd-producng ces n e body and undus o e mas amos aways occur on a background o cronc gasrs w somac are os, e mucosa n s regon s nned, and ruga ods aropy and nesna meapasa. hey exb var yng degrees o are aenuaed. he anrum s reavey spared (unke n H. pyor epea dyspasa, and abou a rd become magnan, especay gasrs). Inesna meapasa s common, and ere s an ncreased ose arger an 2 cm n dameer (see Suppemena eFg. 12.8C). rsk o gasrc cancer. he nlammaory nrae consss many o ympocyes, macropages, and pasma ces (Suppemena eFg. Gastric Adenocarcinoma 12.7). Because o e aropy o e gands, e dsease s aso caed Adenocarcnoma s e mos common magnancy o e somac. Is atropc gastrts, or auommune meapasc aropc gasrs wen ncdence s up o 20 mes ger n Japan and many oer counres meapasa s presen. ousde o Nor Amerca and norern Europe. In e Uned Saes, Clncal Features. Paens presen w sympoms o cronc gasrs, gasrc cancer raes ave dropped by more an 85% durng e 20 cen- bu ony a mnory deveop cncay apparen anema. Serum anbod- ury, presumaby because o reduced exposure o one or more unknown es reacve w parea ces and nrnsc acor are presen n mos carcnogens. here are wo ypes o gasrc adenocarcnomas: nesna paens eary n e dsease. Oten, ere are oer concoman auom- and dfuse. he nesna ype s more common and s assocaed w mune dseases, suc as auommune yrod dsease and dabees. cronc gasrs, nesna meapasa, and dyspasa, wc may be pre- cancerous esons. he dfuse ype as no dened precursor eson and s Peptic Ulcer Disease caracerzed by oss o e umor suppressor E-cadern. This common condition results from excess gastric acid and an impaired mucosal defense, most often the consequence of H. pylori Pathogeness. he deveopmen o gasrc adenocarcnoma s assoc- infection and chronic NSAID use. aed w parcuar muaons and necons; owever, so ar no cear sequence o evens n s deveopmen as been esabsed. Pathoge ne s s. As men one d e ar er, NS AI Ds  n b pros ag  and n    Muaons n e gene encodng E-cadern, an epea nerceu- pro duc  on and  us  mp a r a maj or p a w ay o muc os a  proe c   on , ar adeson moecue, are ound n gasrc carcnomas o e dfuse and H. pyor  d amages  e gas r  c ep e um by  e me can sms ype, bo e rare ama cases and e more common sporadc de a e d pre v ousy. ones. Many sporadc umors n wc e gene s no muaed ave reduced expresson owng o meyaon o e E-cadern promoer. hese observaons sugges a oss o E-cadern s a key sep n e Morphology. Pepc ucers are more requen n e duodenum deveopmen o dfuse gasrc carcnoma. an n e somac. hey are commony ocaed wn a ew cen-    Paens w e ama adenomaous poyposs syndrome ave meers o e pyorc vave n e duodenum or near e nerace muaons n e adenomatous poy poss co (APC) gene, wc o e anrum and e body n e somac. In bo ses, ey are s dscussed aer n e conex o coon cancer. hese paens usuay soar y, sarpy punced-ou deecs (see Fg 2.7, Caper aso are a ncreased rsk or nesna-ype gasrc and duodena 2). he base o bengn ucers s composed o granuaon ssue and cancer. Oer muaons a ave been dened ncude gan- necroc ce debrs and nlammaor y ces resng on a brous scar. o-uncon muaons n e gene or -caenn, a ranscrpon Clncal Features. he dsease s mos oten seen n mdde-aged or acor a s negavey reguaed by E-cadern and APC, and oder adus. Paens usuay presen w epgasrc burnng or pan oss-o-uncon muaons n TP53. ater meas, aoug a sgncan racon presen w GI beedng,    H. pyor–nduced and auommune cronc gasrs are assoc- ron decency anema due o cronc bood oss, or peroraon, wc aed w nesna-ype gasrc cancer, anoer exampe o e nk s a medca emergency. beween cronc nlammaon and cancer (see Caper 5).    Abou 5% o 10% o gasrc adenocarcnomas ave evdence o Tumors of the Stomach Epsen-Barr vrus (EBV) necon. he vrus s cona n suc Masses arsng rom e gasrc mucosa ncude poyps, bengn umors cases, meanng a e umor orgnaed rom an EBV-neced caed adenomas, and magnan umors, o wc e mos common ce, bu precsey ow EBV conrbues o oncogeness n gasrc are adenocarcnomas. cancer s unknown.  CHAPTER 12 Gastrointestinal System 209.e1 Supplemental eFig. 12.7 Autoimmune gastritis. Low-magnification image of gastric body demonstrating deep inflammatory infiltrates, primarily composed of lymphocytes, and glandular atrophy. A B C Supplemental eFig. 12.8 Gastric polyps. (A) Hyperplastic polyp containing corkscrew-shaped foveolar glands. (B) Fundic gland polyp composed of cystically dilated glands lined by parietal, chief, and foveolar cells. (C) Gastric adenoma recognized by the presence of epithelial dysplasia. 210 CHAPTER 12 Gastrointestinal System Neuroendocrine Tumors (Carcinoid Tumors) Morphology. Inesna-ype umors are buky and composed o Mos o ese umors are ound n e GI rac, especay e sma gands w mucn-producng ces a resembe ose n coonc nesne. hey grow more sowy an neuroendocrne carcnomas adenocarcnoma. Grossy, ey can appear as an exopyc mass or (ence e name carcnod) and may come o medca aenon because an uceraed eson w eaped-up margns, unke e “punced- ey secree vasoacve and oer ormone-ke subsances a cause ou” appearance o pepc ucers. Inesna-ype gasrc cancer lusng, sweang, broncospasm, abdomna pan, darrea, and car- predomnaes n g-rsk areas suc as Japan (Fg. 12.4). Dfuse dac vave abnormaes, coecvey known as e carcnod syndrome. umors ave an nrave grow paern, oten wou a dscernbe Wen e umor s nesna, e vasoacve medaors are meabozed mass, and e ces ack nerceuar aderens juncons. he umor n e ver ; ereore, e presence o sympoms usuay relecs mea- ces oten conan arge mucn vacuoes a pus e nuceus o one sac dsease. Foregu neuroendocrne umors (n e somac, duode- sde, producng a “sgne-rng” appearance. hese nrave umors num, and esopagus) rarey spread. Gasrn-producng neuroendocrne may ec a srong broc reacon a convers e wa o e umors, caed gasrnomas, are assocaed w ncreased gasrc acd somac o a eaery conssency, caed nts pastca. producon, causng ucers (Zonger-Eson syndrome). Mdgu carc- nod umors (sma nesne) are oten mupe and aggressve. Hnd- gu carcnod umors (appendx and coon) are usuay ncdena and Clncal Features. he mos common sympoms a e me o na bengn. Hsoogcay, a o ese umors conan unorm-appearng presenaon are abdomna pan, dyspaga, and weg oss. Occu ces w abundan granuar cyopasm (Suppemena eFg. 12.10). beedng s requen and may cause ron decency anema. Gasrc cancers spread ocay o nvove e duodenum, pancreas, and rero- Gastrointestinal Stromal Tumor peroneum. Measases occur n regona ymp nodes and n dsan Gasronesna sroma umor (GIST) s e mos common mesency- organs, and wen presen ndcae a poor prognoss. ma umor o e abdomen, and over a occur n e wa o e som- ac. I arses rom e gasrc pacemaker ces known as nersa ces o Gastric Lymphoma Caja. O ese umors, 75% o 85% conan acvang muaons n e he somac s a common se or exranoda ympomas, wc gene encodng e yrosne knase KIT, wc uncons as e recepor accoun or neary 5% o gasrc magnances. Gasrc ympomas are or sem ce acor. Anoer 8% o umors ave acvang muaons n o B-ce orgn and many occur n wo orms: ndoen margna zone e reaed paee-derved grow acor (PDGF) recepor, aso a yro- ympomas a reman ocazed o e somac or ong perods and sne knase; ese wo muaons are muuay excusve, because ey bo are srongy assocaed w H. pyor necon, and aggressve, dfuse acvae e same sgna ransducon paway. he consuve knase sg- arge B-ce ympomas (Suppemena eFg. 12.9). Bo are dscussed nang smuaes unreguaed ce proeraon. In GISTs wou KIT or urer n Caper 9 PDGFRA muaons, genes encodng componens o e mocondra A B C D Fig. 12.4 Gastric adenocarcinoma. (A) Intestinal-type adenocarcinoma consisting of an elevated mass with heaped-up borders and central ulceration. (B) Intestinal-type adenocarcinoma composed of columnar, gland-forming cells infiltrating through desmoplastic stroma (C) Linitis plastica. The gastric wall is markedly thickened and rugal folds are partially lost. (D) Signet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent-shaped nuclei.