j0305257 Systematic pathology practice GIT PATHOLOGY j0305257 GIT přehled j0305257 ORAL CAVITY j0305257 Congenital disorders: hare-lip and cleft palate ûincidence 1 : 950 newborns ûlateral cleft – isolated or complete ð fusion defect of the first branchial arch –maxilar process with fronto-nasal lateral process û genetic x acquired (environmental) û unilateral x bilateral û ðcheiloschisis (upper lip) – complete/incomplete ðgnathoschisis (jaw) ðpalatoschisis (hard palate) ðuranoschisis (soft palate) ðstaphyloschisis (uvula) ð ûmedial, oblique, transverse cleft (rare) • • j0305257 Cheilognathopalatoschisis ANd9GcREIsR_t5fTg7UPVs-cnXZRB1zNYdSZuYgPdAFwK0Jdjvai92D8 copy j0305257 Salivary glands û3 pairs of large major salivary glands, numerous small ones ûserous / mucinous ûsecretory units → glandular ducts ûdouble cell layer – external myoepithelia ûtumors mostly in the parotid gland, in adults usually epithelial tumors û j0305257 slinné žlázy anatomie j0305257 Salivary gland tumors û parotid ðcca 75%, mostly benign (70-85%) û submandibular ð 40% malignant ûminor salivary glands ð50% malignant ûsublingual ðmostly malignant j0305257 Histologic types ûSelected types û pleomorphic adenoma (benign mixed tumor) û adenolymphoma (Warthin tumor) û oncocytoma û mucoepidermoid carcinoma û adenoid cystic carcinoma û malignant mixed tumor j0305257 Pleomorphic adenoma (mixed tumor of salivary glands) û former name „myxochondroepithelioma“ û benign epithelial tumor û 80% in the parotid gland, most common parotid tu û any age, mostly middle-late adult age û slow-growing firm mass û well-demarcated, but capsule incomplete ûfrequent recurrences after incomplete resection ûlow risk of malignant transformation (4%), in long duration, recurrences û j0305257 Pleomorphic adenoma û ûmicro: ðhistologic diversity ðductal and myoepithelial tumor cells ðepithelial elements in strands or sheets ðmyxoid to chondroid stroma produced by myoepithelia ðoften penetrates the capsule → protuberances û j0305257 Pleomorphic adenoma _parotis-mixed-tumor-307c j0305257 Pleomorphic adenoma pleiomorfni adenom 40x 01 1 1 myxoid stroma 2 epithelial strands and sheets j0305257 Warthin‘s tumor (cystadenolymphoma) û5-10% of total salivary gland tumors, benign ûM> F, 6th-7th decade ûlower pole of the parotid gland ûlow recurrence rate, malignant transformation (ca, malignant lymphoma) highly uncommon ûrisk factors: ðsmoking (8x), radiation, EBV ûorigin? (heterotopic salivary tissue in a LN; reactive epithelial proliferation + lymphocytic infiltration) ûhistology: ðcystic or cleftlike spaces with double-layered epithelial lining, dense lymphoid stroma (usually + germinal centers) j0305257 Warthin-ma Warthin‘s tumor (cystadenolymphoma) j0305257 Warthin‘s tumor (cystadenolymphoma) 1 double-layered epithelium 2 lymphoid stroma 1 2 j0305257 Tonsillitis chronica ûrecurrent chronic inflammation ûacute exacerbations - enlarged, red, swollen painful tonsils ûgross: ðmostly purulent exudate with necrotic epithelial cells and bacteria in crypts forming semi-firm foul-smelling debris ðpseudomembranous tonsillitis (diff. dg. x EBV) ð j0305257 Tonsillitis chronica û complications: local, distant ð phlegmonous acute tonsillitis (necrosis and ulceration, penetration of bacteria into the interstitium→ inflammation may progress into retrotonsillar stroma) ðabscessi (tonsillar, peritonsillar, retropharyngeal) + spread ðdistant – rheumatic fever, glomerulonephritis û micro: ðreactive hyperplasia of lymphoid tissue, lacunae filled with neutrophils, debris and bacteria, local fibrotisation û û j0305257 Tonsilla palatina chronic purulent inflammation 1 1 2 2 3 3 1 squamous cell epithelium in the lacuna 2 detritus with neutrophils 3 germinal centers 4 ulceration 4 j0305257 Precanceroses and tumors ûmostly epithelial, less commonly mesenchymal lesions ûsequence ð normal tissue – hyperplasia – dysplasia – CIS – invasive carcinoma ûrisk factors ð smoking, alcohol, their combination; irradiation, HPV, betel, other chronic irritation j0305257 Squamous cell carcinoma elevated/ulcerated firm lesion copy j0305257 Esophageal diverticula û ûdiverticulum – an acquired outpouching of the esophageal wall involving all the layers of the wall (true diverticulum) û ûZenker‘s diverticulum (pharyngoesophageal) - most common type, located on the posterior wall in the pharyngoesophageal junction, weakening of m. constrictor pharyngis, developed by pulsion (forcible distension of the esophagus) → pulsion diverticulum û ûMidthoracic diverticulum - in the mid-chest; developed by traction (external forces pulling on the wall - inflammation with scarring e.g.) → traction diverticulum û ûEpiphrenic diverticula - above the diaphragm û ûSigns: dysphagia, regurgitation, foetor ex ore û ûComplications: putrid inflammation, ulceration, perfortion into mediastinum j0305257 Esophageal varices ûcongested and dilated submucosal veins in the distal third of the esophagus ûin portal hypertension ûporto-caval anastomoses ûcomplications - rupture with massive hemorrhage into the lumen, haematemesis, haemorrhagic shock j0305257 Esophageal varices - endoscopy û û û û û û û û û copy û jícnové varixy j0305257 G:\makro foto k úpravě\6.png Esophageal varices gross j0305257 Mycotic oesophagitis ûcandida, aspergillus, mucor, cryptococcus û ûsuperficial form low-level immunodeficiency, patients on broad-spectrum ATB or corticosteroids therapy, diabetics, pregnancy… û ûgeneralised form + secondary deep mycotic infections – high-grade immunodeficiency - AIDS, neoplasia (haemathologic), immunosuppression, debilitated patients j0305257 Mycotic oesophagitis ûgross: ðwhite to gray pseudomembranes with hemorrhagic bases after removal ûmicro: ðnecrotic mucosa with mixed inflammatory infiltrate, numerous fungal organisms (pseudo/hyphae, yeasts) ûspecial impregnation/staining for detection of the fungi (Groccott, PAS, Giemsa) j0305257 Mycotic oesophagitis mykoticka ezofagitida 100x j0305257 Mycotic oesophagitis (Groccott silver impregnation) mykoticka ezofagitida Grocott 100x j0305257 Mycotic oesophagitis - detail (PAS staining) mykoticka ez 200x j0305257 Mycotic oesophagitis - detail (PAS staining) mykoticka ez 400x j0305257 Reflux oesophagitis ûchemically caused inflammation in gastro-oesophageal reflux disease (sq. epithelium sensitive to acids) ûsigns x pathology – low correlation ð heartburn, dysphagia ûgross: ðmucosal hyperemia, epithelial erosions, ulcerations, scarring, stenosis ûmicro: ð3 reactive alterations of the squamous cell epithelium: basal zone hyperplasia, elongation of lamina propria papillae, inflammatory infiltrate with eosinophils. ûcomplication: Barrett‘s oesopagus (predisposition to maligancy)! û j0305257 Reflux oesophagitis esophagitis02 Regular oesophageal epithelium Reflux oesophagitis: basal zone hyperplasia (>20%), elongation of lamina propria papillae (into the superficial 1/3) j0305257 Barrett‘s oesophagus ûcomplication of reflux oesophagitis ûrisk for the development of adenocarcinoma! ûreplacement of the normal squamous cell epithelium by columnar epithelium with goblet cells (= intestinal metaplasia) → risk of dysplasia û→ oesophageal adenocarcinoma (so-called Barrett‘s carcinoma) j0305257 Barrett‘s oesophagus Barrett 1 regular oesophageal mucosa 2 metaplasia 3 gastro-oesophageal junction 4 cardia 1 copy 2 3 4 j0305257 Barrett‘s oesophagus û1 3 proprie s překrvením û Barrettův jícen 100x 001 1 2 3 j0305257 Barrett‘s oesophagus Barrettův jícen 100x 002 1 intestinal type epithelium 2 goblet cell 3 squamous cell epithelium 1 2 3 j0305257 Barrett‘s oesophagus PAS ALC staining – blue goblet cells Barrett 100x 02 j0305257 Barrett‘s oesophagus - dysplastic epithelium BJ02 2 high grade dysplasia 2 2 2 1 1 1 low grade dysplasia j0305257 û usually in the mid-third of the esophagus û M>F, >45 yrs of age û Risk factors: ðcarcinogenic substances in food (aflatoxin, nitrosamines), tobacco, alcohol, HPV, very hot beverages, chronic inflammation û Symptoms: ðdysfagia, weight loss, cachexia Squamous cell carcinoma of the oesophagus j0305257 û û gross: ðpolypoid exophytic mass, ulcerative or diffuse infiltrative neoplasm û û bad prognosis: ð tendency to spread through submucosal lymph vessels → distant satellite tumor foci û Squamous cell carcinoma of the oesophagus j0305257 Squamous cell carcinoma of the oesophagus Obrázek2.jpg Obrázek1.jpg 1 esophagus 2 cardia 3 fundus 4 body 5 antrum 6 pylorus 7 tumor 1 2 3 4 5 6 7 _esophagus-sq-cell-ca-detail 1 2 7 copy j0305257 Squamous cell carcinoma of the oesophagus Cajicnu 1 keratinisation arrows -mitoses 1 j0305257 STOMACH j0305257 žaludek anat j0305257 žaludeční sliznice přehled j0305257 Gastritis ûtwo general types: ðacute - acute mucosal inflammatory process of a transient nature, ð causes: salt, spices, alcohol, NSAIDs, stress, infection •gross: • hyperemic, oedematous mucosa with erosions, haemorrhage •micro: • hyperemia, oedema, neutrophilic (foveolar) inflammatory infiltrate, erosions j0305257 Gastritis ð ðchronic - chronic inflammatory changes leading to mucosal atrophy and epithelial metaplasia • usually associated with Helicobacter pylori •micro evaluation: »inflammatory infiltrate in lamina propria mucosae - lymfoplasmocytic (grade of chronicity) + neutrophils (grade of activity) »presence of HP (+/-) and quantitative analysis »presence of atrophy, intestinal metaplasia (complete, incomplete) and possible dysplasia û j0305257 Clinical-pathological classification of chronic gastritis 1)Chronic non-atrophic gastritis (superficial) („B“) 2) 2)Chronic atrophic gastritis I.Autoimmune gastritis („A“) II.Chronic multifocal atrophic gastritis III. û3) Special forms (chemical - reactive, lymphocytic, eosinophilic, granulomatous) I. û j0305257 Clinical-pathological classification of chronic gastritis ûChronic non-atrophic gastritis (superficial) û ðHelicobacter pylori •gross: antrum and body mucosa •micro: superficial or deep inflammation, active chronic gastritis, lymphocyte and plasma cell response forming lymphatic follicles in the glandular area, final mucosal atrophy •higher risk of developing NHL j0305257 Chronic non-atrophic gastritis - follicular 1 antral mucosa 2 muscularis mucosae 3 submucosa 4 lymphatic follicles with germinal centers 1 1 2 2 3 4 j0305257 Chronic non-atrophic gastrits - detail of the mucosa HLO+ gastritis 19-12 100x 1 mixed inflammatory infiltrate in lamina propria mucosae 2 gastric pit 1 2 j0305257 Chronic active gastritis - grade of activity 2 _s4-3a-gastritis32-40x-he intraepithelial neutrophils j0305257 Chronic non-atrophic gastritis Helicobacter pylori (Warthin-Starry) j0305257 Chronic non-atrophic gastritis Helicobacter pylori (Giemsa–Romanowski) HLO+ gastritis 19-12 400x j0305257 Chronic gastritis ûChronic atrophic gastritis û1/ Autoimmune chronic atrophic gastritis („A“) û ðautoimmune, anti-parietal cell and anti-intrinsic factor antibodies, hypochlorhydria, association with vitamin B12 deficiency and pernicious anemia •gross: mucosa of the gastric body and fundus atrophy •micro: chronic non-active gastritis (severe mucosal atrophy with intestinal or pseudopyloric metaplasia, fibrosis) •higher risk of developing adenocarcinoma! û j0305257 Chronic gastritis ûChronic atrophic gastritis û2/ Chronic multifocal atrophic gastritis (pangastritis) û ðHelicobacter pylori-associated ðlow grade of inflammation (body + antrum) ðepithelial reactive changes, erosions ðuneven distribution of atrophic foci û û û û û j0305257 Chronic atrophic gastritis (gastric body) atroficka gastritida, metapl.jpg 1 inflammatory infiltrate 2 pseudopyloric metaplasia 3 intestinal metaplasia total glandular atrophy 2 1 3 1 j0305257 Chronic atrophic gastritis (gastric body) telo zaludku s metaplazii.jpg 1 gastric glands 2 pseudopyloric metaplasia 2 1 2 j0305257 gastritis06 Chronic gastritis - intestinal metaplasia 1 enterocytes 2 goblet cells 3 Paneth cells 2 1 3 1 1 j0305257 Chronic gastritis ûSpecial forms: û ûChemical (reflux) gastritis / reactive gastropathy (former „C“) ðbile reflux, duodenal reflux after partial gastrectomy, NSAIDs ðmicro: hyperemic, oedematous mucosa, foveolar hyperplasia, vasodilatation, little inflammatory response û ûLymphocytic, eosinophilic, granulomatous... j0305257 Reactive gastropathy (gastritis C) mild changes reaktivni gastropatie lehka 2.jpg 1 serrated foveolar pattern 2 vasodilatation 1 2 2 j0305257 Reactive gastropathy (gastritis C) severe changes reaktivni gastropatie tezka.jpg 1 serrated foveolar pattern 2 reduced mucous production 3 vasodilatation 4 epithelial reactive changes 1 2 4 3 j0305257 Hypertrophic gastropathy û û ûuncommon, large mucosal folds ðmarked epithelial hyperplasia (↑ growth factor release), may mimic a tumor: •Ménétrier‘s disease (hyperplastic hypersecretory gastropathy with protein loss) •hypersecretory gastropathy (hyperplasia of parietal and chief cells) •glandular hyperplasia in Zollinger - Ellison syndrome (in neuroendocrine tumors with gastrin production) û j0305257 Gastric erosions ûdefinition: ðlimited by m. mucosae, tiny superficial defects < 3 mm ûcauses: ðNSAIDs, alcohol, vomiting, stress, burns, infection ûlocalisation: ð antrum and body ûmicrocirculation disorder, capillary rupture ûcomplete regeneration within a few days û j0305257 Peptic ulceration ûUlcer definition: mucosal defect progressing through the m. mucosae into the submucosa or deeper ûrisk factors/causes: ðgeneral: genetics, age, stress, alcohol, smoking ðlocal: gastric hyperacidity, HP gastritis, NSAIDs ûlocalisation: ðpylorus, lesser curvature, bulbus duodeni, (Meckel‘s diverticulum, stomic junction, GE junction) ð j0305257 Gastric ulceration ûAcute ulcer: ð sharply demarcated defect 4 - 25mm; acute gastritis, severe stress (shock, trauma, burns), NSAIDs, severe hyperacidity ûChronic ulcer: ðslightly overhanging margins, radial adjacent mucosal folds ðgross: smooth base ð4 histologic zones: 1) fibrinoid necrosis and cell debris – active u. 2) mixed inflammatory infiltrate 3) granulation tissue 4) fibrous scar ðcomplications: bleeding (overt, occult), penetration, perforation, scarring + obstruction, rare malignant transformation j0305257 chron Copy Chronic peptic ulcer of the stomach j0305257 Image019 Perforated duodenal ulcer j0305257 Image020 j0305257 Chronic peptic ulcer of the stomach - basis he40x 1 surface – cell detritus 2 narrow capillary lumina (compressed by proliferating tissue) 3 granulation tissue with inflammatory infiltrate and fibrous tissue 4 fibrinoid necrosis 1 2 3 3 2 2 4 3 j0305257 Peptic duodenal ulcer - edges of the ulcer pepticky vred duodena 100x 1 ulcer margin 2 residual mucosa 3 ulcer basis 4 duodenal Brunner‘s glands 1 2 3 j0305257 Chronic peptic duodenal ulcer - basis of the ulcer pepticky vred duodena 200x 1 inflammatory infiltrate 2 fibrinoid necrosis of the artery wall 3 basis of the ulcer 1 1 3 j0305257 Important gastric tumors û PSEUDOTUMORS ðnon-tumorous polyps (inflammatory, hyperplastic, fundic gland polyps) ð û EPITHELIAL ðadenoma (in the setting of chronic gastritis/intest. metaplasia) ð malignant: carcinoma (adenoca, neuroendocrine ca, …) - û NON-EPITHELIAL ðgastrointestinal stromal tumors (GISTs) ðlymphomas (NHL: MALT, DLBCL) û û û û û j0305257 Gastric carcinoma ûmost common malignant gastric tumor ûlocation: antrum, pylorus, lesser curvature ûrisk factors: ðprecursor lesions: chronic gastritis with intestinal metaplasia, infection with HP, intraepithelial neoplasia ðEBV, dietary carcinogenes (salted, smoked food), familial ûclinical features: ðvomiting, abdominal discomfort, weight loss, anorexia ð Direct spread into adjacent organs/tissues • Metastases: LN regional, distant (Troisier‘s supraclavicular LN), portal circulation (liver), peritoneal dissemination, lung, ovarian Krukenberg tumor in females. j0305257 Gastric carcinoma ûClassification: û ûmacroscopical: ðexophytic (polypous) ðexcavated (ulcerated) ðinfiltrative (linitis plastica) ûdepth of invasion: ðearly: only in mucosa and submucosa ðadvanced: extended into the muscular wall ûhistological type ð ð j0305257 WHO histological classification of gastric tumors ûTubular ûPapillary ûMucinous ûSignet-ring cell ûAdenosquamous ûSquamous ûUndifferentiated ûNeuroendocrine j0305257 Lauren’s histological classification ûIntestinal: ð50%, HP chronic gastritis, ↓ tendency ðintestinal metaplasia-connected, neoplastic tubular glands/papillary formations, columnar epithelium, expansive growth ð> 50 yrs, M:F 2:1 ûDiffuse: ð30%, ↑ tendency ðdissociated cells infiltrating singly / in small clusters into the stomach wall, signet-ring cells possible, reactive desmoplasia - fibrosis (scirrhus) ðearlier age, M:F 1:1 ûMixed ð j0305257 Gastric adenocarcinoma - exophytic growth _stomach-adenocarcinoma-381 copy j0305257 Gastric adenocarcinoma - intestinal type _s4-5-carc-10x-he 1 normal gastric mucosa 2 tubopapillary adenocarcinoma 3 muscularis mucosae line - sharp demarcation of the tumor from normal mucosa 1 2 3 j0305257 Gastric adenocarcinoma (intestinal type) – infiltration into lamina muscularis propria _s4-5-carc-40x-he 1 tumor cells 2 smooth muscle cells 1 2 j0305257 _stomach-carcinoma-diffuse-381 Gastric adenocarcinoma - diffuse type copy j0305257 Gastric adenocarcinoma - diffuse type _s4-6-zaludek-dif-ca-10x-he 1 intestinal metaplasia of the mucosa 2 diffuse infiltration with signet-ring cells 1 2 j0305257 Gastric adenocarcinoma - diffuse type – infiltration into lamina muscularis propria û adenoca prsténčité bb 40x 1 signet-ring cells infiltrating the muscular wall 1 j0305257 Gastric adenocarcinoma - diffuse type detail adenoca prsténčité bb 200x 01 1 signet-ring cells infiltrating the muscular wall 1 j0305257 _s4-6-ca-diff-zaludek-40x-pas Gastric adenocarcinoma - diffuse type detail (PAS) Signet-ring cells j0305257 Image091 Krukenberg tumor copy j0305257 Krukenberg tumor ovaryslide%2017 copy j0305257 Gastrointestinal stromal tumors (GISTs) ûmesenchymal tumors ûarising from intestinal cells of Cajal (pacemaker cells controlling peristalsis) ûorigin anywhere in the GIT: predominantly the stomach and small intestine ûspindle-like or epitheloid cells, IHC CD117+, ûbiologic behaviour prognosis : ðaccording to mitotic rate, size, localization j0305257 Oesophageal GIST GIST 20x 01 j0305257 Oesophageal GIST - detail (spindle-like cells, low malignancy) GIST 100x j0305257 Oesophageal GIST - detail (spindle-like cells, highly malignant) GIST maligní 100x 01 j0305257 Intestinal GIST - detail (spindle-like cells, highly malignant) GIST maligní 400x j0305257 Intestinal GIST IHC CD117 positivity GIST maligní 200x CD117 j0305257 INTESTINES j0305257 Normal mucosa of the small intestine ûvilli to crypts height ratio 3:1 – 5:1 ûstandard number of intraepithelial lymphocytes: 40 IEL / 100 enterocytes û ðbrush border – microvilli (PAS+, alkaline phosphatasis +) ðdifferentiated enterocytes j0305257 Normal villi of the small intestine 6 j0305257 Malabsorption syndromes ûa group of symptoms resulting from an û alteration in the digestion / absorption of nutrients mostly in the small intestine û symptoms: ðanorexia, diarrhea, steatorrhea, weakness, weight loss, abdominal distention, ðgrowth disturbances, eczema, neurologic/psychologic disturbances, bleeding disorders, anaemia, tetany ð ûdisturbance of: ðdigestion intraluminal, terminal in the brush border ðmucosal absorption - enterocytes abnormalities, reduced intestinal surface area ðlymphatic transport ð j0305257 Malabsorption syndromes û Classification ð primary – enterocytes‘ disorder (inborn, acquired) ðsecondary – cause apart from enterocytes û commonly mixed causes j0305257 Defects of mucosal absorption ûBrush border enzymatic deficiency (lactose intolerance – lactase deficiency) û ûCeliac disease gluten (gliadin)-sensitive enteropathy j0305257 Celiac disease û ûprevalence 0,5-1% in Caucasian Europeans ûassociated with dermatitis herpetiformis Duhring, DM I., Sjögren sy, etc. ûimmunological sensitivity to gluten (component of wheat) ûantibodies EMA, ARA, TG (non-specific anti-gliadin) ûgenetic (HLA), immune, exogenous factors j0305257 Celiac disease ûgluten-free diet necessary, sm. lifelong ûrisk of malignant disease: ðmalignant lymphomas (T-cell), carcinomas of the small intestine ûclinical ðinfancy (6-24 m.), adults 30-60 yrs; silent, latent ûsymptoms: ðirritability, diarrhoea, fatigue… ûendoscopy: ðloss of mucosal folds, mosaic mucosal pattern, prominence of the submucosal vessels û j0305257 Celiac disease ûmicro: most changes in the proximal part of the small intestine ûbasic histologic features: ðincreased number of intraepithelial T-cells ðinflammatory infiltrate (plasma cells, eosinophils, neutrophils, T-cells) in lamina propria mucosae ðvillous atrophy ðreactive hyperplasia (elongation) of the crypts û j0305257 Marsh classification 0-IV ûStage 0: normal mucosa ûStage I: infiltrative ð increased number of IEL ûStage II: hyperplastic ð proliferation of the crypts ûStage III: destructive ð villous atrophy ûStage IV: hypoplastic ð crypt hypoplasia, loss of villi j0305257 Celiac disease û IEL – specific activated CD8+ T-cell subpopulation û direct cytotoxic activity – killing of enterocytes û increased enterocytes‘ turnover û non-specific histology – diff. dg. alimentary allergies, viral infections, giardiasis, tropical sprue j0305257 Celiac disease Marsh I j0305257 Celiac disease Marsh IIIc 1-upr j0305257 Celiac disease atrophic mucosa - detail 1 1 Povrch ulcerace – buněčný dateritus 2 Fibrinoidní dystrofie vaziva 3 Chronicky zánětlivě infiltrovaná granulační tkáň 4 Chronický zánět v lamnina propria (sliznice na periferii vředu) 2 3 3 3 4 2 1 Total villous atrophy 2 Increased number of intraepithelial lymphocytes and dedifferentiated enterocytes 3 Goblet cell 3 2 1 1 1 2 j0305257 Inflammatory bowel disease (IBD) û idipathic, chronic relapsing inflammatory disorders of not completely known origin ûgenetic predisposition, immunologic factors û etiology: ðaberrant local immune response to exogenous stimulus (microbiome)→ increased transepithelial permeability → inflammation acceleration û Crohn disease û Ulcerative colitis û Indeterminated colitis (10-15%) j0305257 IBD ûcommon histologic features: û 1)abnormal crypt architecture 2)crypt atrophy 3)dense inflammatory infiltrate in lamina propria, basal plasmacytosis 4)Paneth cell metaplasia in the left colon j0305257 Crohn‘s disease ûClinical features: ðrecurrent attacks of diarrhea, abdominal pain, fever ðabrupt beginning, lasting days to weeks, symptom-free intervals, ðcommon other AI diseases: •iritis, ankylosing spondylitis, erythema nodosum, PSC ûGross: ðterminal ileum, or anywhere else in the GIT (oral-anus) ðsharply demarcated , segmental lesions and skip lesions: •shallow → longitudinal ulcers •wall stenosis and thickening, fissuring, fistulae ð ð j0305257 Crohn‘s disease ûHistology: ð transmural inflammatory infiltrate ð formation of lymphatic follicles/germinal centres ð non-caseating granulomas (not always present) in submucosa, subserosa and regional lymph nodes ð fissuring, ulceration ð fibrosis j0305257 Crohn‘s disease ûComplications: ðnarrowed lumen, intestinal strictures, obstruction ðmalabsorption, protein loss ðperforation, peritonitis, fistulae formation ðhemorrhage ðsystemic AA amyloidosis ðcarcinoma û j0305257 Crohn‘s disease Image027 j0305257 Crohn‘s disease crohn copy j0305257 Crohn‘s disease in the colon (transmural chronic inflammatory infiltrate) 20x2 1 Transmural inflammatory infiltrate 2 Intestinal mucosa 3 Serosa 3 2 1 1 1 j0305257 Crohn‘s disease - Enteritis regionalis fisura40x 1 1 Fissure in the mucosa 2 Crypt without dysplastic changes 3 Dense chronic inflammatory infiltrate 3 2 j0305257 Crohn‘s disease inflammatory infiltrate in the submucosa MC 20x 1 Mucosal architectural disarray 2 Submucosa with oedema and inflammatory infiltrate 3 Dilated submucosal vessels 1 2 3 j0305257 Crohn‘s disease inflammatory infiltrate in the subserosa MC 20x 02 1 Muscularis propria 2 Expanded subserosa with inflammatory infiltrate 1 2 j0305257 Crohn‘s disease - granuloma in the submucosa 8 1 Multinucleated giant cell 2 Granuloma in the submucosa 3 Inflammatory infiltate in the submucosa 4 Muscularis propria with inflammatory infiltrate 1 1 2 3 4 j0305257 Crohn‘s disease - inflammatory infiltrate 13 1 1 Lymphatic follicle in the subserosa j0305257 Ulcerative colitis ûClinical features: ð relapsing attacks of bloody mucoid diarrhea, cramps, lower abdominal pain ð start - rectum + sigmoid, continuous retrograde extension, may affect the entire colon (pancolitis) ð unclear etiology, autoimmune and genetic factors, variable triggers ð associated with systemic disorders (eye, skin, joint, bile tract – primary sclerosing cholangitis) ûGross: ð hyperemia, oedema, flat ulcerations, regenerative hyperplastic mucosa forming pseudopolyps j0305257 Ulcerative colitis ûMicro: ð non-specific inflammatory infiltrate only in the mucosa and submucosa ð crypt abscesses, crypt destruction ð no granulomas, no skip lesions ð very little fibrosis, no mural thickening ð high risk of carcinoma development j0305257 Ulcerative colitis ûMicroscopic phases of the inflammation: ð1. active • hyperemia, mixed inflammatory infiltrate, crypt abscesses ð2. healing • less neutrophils, no crypt abscesses, epithelial regeneration ð3. remission • mucosal architectural disarray, atrophy, inflammatory changes sm. only in the rectum ûComplications: ðtoxic megacolon, hemorrhage, perforation, peritonitis, carcinoma development j0305257 Ulcerative colitis - gross GI071 copy j0305257 Ulcerative colitis superficial inflammatory infiltrate 14 3 1 Mucosa with focal normal epithelium 2 Inflammatory infiltrate in the mucosa and submucosa 3 Muscularis propria 4 Mucosa ulceration 2 2 4 1 3 2 4 1 j0305257 Ulcerative colitis - crypt abscess 1 Crypt abscess 2 Inflammatory infiltrate in the lamina propria 3 Lamina muscularis mucosae 3 2 1 j0305257 Ulcerative colitis - dysplastic changes in the epithelium 17 1 Dysplastic changes in the epithelium 2 Mixed inflammatory infiltrate 2 1 j0305257 Ulcerative colitis UC 20x 1 1 Mucosal architectural disarray 2 Inflammatory infiltrate in the mucosa and submucosa 3 Ulceration 2 3 j0305257 Ulcerative colitis basal plasmacytosis UC bazální plazmocytóza 400x j0305257 Ulcerative colitis basal plasmacytosis UC bazální plazmocytóza j0305257 Ulcerative colitis Paneth cell metaplasia in the left colon UC Panet bb 400x j0305257 Ulcerative colitis epithelial dysplasia UC dyspl 100x 1 1 Ulcer in the mucosa 2 Inflammatory infiltrate in the mucosa 3 LG epithelial dysplasia 2 3 3 j0305257 Further types of enterocolitis û pseudomembranous û ischemic ðshort-term decreased blood supply to the intestine (shock, trauma, surgery) û microscopic (collagenous, lymphocytic) ðchronic watery diarrhea, normal colonoscopy, associated with autoimmune diseases û infectious û postradiation û others j0305257 Pseudomembranous colitis ûetiology: ðinfection – bacterial (Clostridium difficile, Salmonella, Staph. aureus) ðantibiotic-associated ðuremia ûgross: ðgreyish pseudomembranes on the mucosal surface, ulcers ûmicro: ðfibrinous pseudomembrane with neutrophils, bacteria and macrophages, adherent to the necrotic mucosa j0305257 Pseudomembranous colitis ûEndoscopy (copy) PseudoMembranousCol5 j0305257 Pseudomembranous colitis PMC 40x 1 Mucosa with focally normal epithelium 2 Residual necrotic mucosa 3 Pseudomembrane 1 2 3 j0305257 Pseudomembranous colitis - detail PMC 100x j0305257 Pseudomembranous colitis (Clostridium difficile etiology) klostridiova PMC 40x 2 1 1 Pseudomembrane with bacterial colonies 2 Residual mucosa j0305257 Ileus – intestinal obstruction/disruption of the normal motility ûmechanic (strangulation, obturation) ðAdhesions ðhernias ðvolvulus ðinvagination ðtumors ðobstruction (foreign body) ðcongenital atresia ðmeconial in cystic fibrosis ûdynamic ðparalytic: toxic-infective, drugs, peritonitis, post-operative ðvascular: hemorrhagic infarction ðmyopathy, neuropathy ðHirschprung‘ disease û j0305257 Ileus ûClinical features: signs of „acute abdomen“ with acute pain, cramps, abdominal distention, nausea and vomiting, stop of the stool/gases passage û Type / severity of the signs acccording to localisation + stage of obstruction û ûIntestinal wall in/above the obstruction: û dilatation → inflammation → (peritonitis, sepsis) → mural necrosis → perforation → stercoral (fecal) peritonitis j0305257 Image042 Volvulus, bowel infarction j0305257 Image040 Gallstone ileus j0305257 ischemic1321322667378 Hemorrhagic infarction of the intestine ûresult of intestinal ischemia copy j0305257 Hemorrhagic infarction of the intestine hem infarzace streva 20x 1 Complete transmural hemorrhagic necrosis of the intestinal wall 1 1 1 j0305257 Hirschprung‘ disease Image044 j0305257 Intestinal polyps û Non-neoplastic polyps ðhyperplastic polyp (<5 mm) minimal malignant potential, part of group of serrated lesions ðjuvenile polyp - hamartoma; in children under 5 years, in the rectum, sporadic or part of juvenile polyposis sy (AD, haemorrhage, ↑ risk of ca) ðPeutz - Jeghers hamartoma polyps + mucocutaneous hyperpigmentation; single/multiple (P-J syndrome - ↑ risk of pancreatic, pulmonary, ovarian, breast cancer) ð j0305257 Intestinal polyps ûNeoplastic sporadic adenomatous polyps û ðtubular adenoma (smaller, spheric, pedunculated) ðvillous adenoma (large, flat, sessile, often HG dysplasia and high malignant potential) ðtubulovillous adenoma • j0305257 Familial syndromes û û 1/ Familial hereditary polyposis syndromes ðfamilial adenomatous polyposis (FAP): ð AD, mutation of suppresor APC gene, 100-2500 colonic adenomas, teenagers, 100% risk of cancer ðGardner syndrome: FAP variant, dental anomalies ð extraintestinal tumors: osteomas, gliomas, lipomas, fibromas ðPeutz - Jeghers syndrome : ð melanotic mucosal and cutaneous pigmentation with hamartomatous intestinal polyps j0305257 ð ð2/ Lynch syndrome ð(hereditary non-polyposis colorectal cancer, AD), DNA mismatch repair defect + increased rate of mutations; younger age, right colon. ðIncreased risk of multiple tumors of the stomach, small intestine, liver, gallbladder tract, urinary tract, brain, skin, prostate. û j0305257 Serrated lesions û û ð special heterogenous group of polypous lesions, serrated (sawtooth, stellate) morphology, part of intraepithelial neoplasias ð precursors of perhaps one third of colorectal cancers ð classification: dysplastic, non-dysplastic û û j0305257 Classification of serrated lesions/polyps û Non-dysplastic ðhyperplastic polyp ðsessile serrated adenoma/polyp û With dysplasia ðsessile serrated adenoma/polyp w. dysplasia ðtraditional serrated adenoma ð 12819-11-100x 11913-2-200x 02 j0305257 Colon – hyperplastic polyp 12819-11-100x 1 Hyperplastic epithelium 2 Enterocytes 3 Goblet cells 1 2 3 j0305257 Colon - juvenile polyp 20x 1 Inflammatory exudate in dilated cystic crypt 2 Tubular structures with normal regular colonic epithelium 2 1 2 j0305257 Colon - hamartomatous P-J polyp 33 1 Stroma of the polyp 2 Superficial epithelium 2 1 2 j0305257 Adenomas copy j0305257 Polyposis of the colon polyposa copy j0305257 Tubular adenoma 37 1 2 3 1 Tubular adenoma with low grade dysplasia 2 Border between dysplastic and normal epithelium 3 Lamina muscularis mucosae 4 Normal intestinal epithelium 4 j0305257 Tubular adenoma – low grade dysplasia 39 j0305257 Tubular adenoma – high grade dysplasia 43 j0305257 Villous adenoma vilosní adenom copy j0305257 Villous adenoma j0305257 Colorectal carcinoma û high incidence in the Czech Republic and other developed countries û 60 - 70 % in the rectum and sigmoid (50% detectable by per rectum examination) û Risk factors: lifestyle + diet, smoking, alcohol ðhigh intake: refined carbohydrates, fat, red meat ðdecreased intake: unabsorbable vegetable fiber, protective micronutrients (vtamins A,C,E) ûpredisposing factors: genetic ðpolyposis ðulcerative colitis ð j0305257 Colorectal carcinoma ûGross: ð exophytic, polypous • proximal colon - long time asymptomatic ð endophytic, ulcers with heaped-up edges • distal colon - early stenosis ð annular • encircling lesions ðinfiltrative • rare, linitis plastica type • • j0305257 Colorectal carcinoma ûMicro: ðtubular adenocarcinoma (most frequently) ðother adenocarcinoma types: • cribriform comedo-type • micropapillary • medullary • mucinous • serrated • signet ring cell ðadenosquamous, spidle-like, squamous cell, undifferentiated û j0305257 Colorectal carcinoma ûTNM classification and tumor progression: ðpTis intraepithelial/intramucosal (100% 5-year survival, no metastases) ðpT1 submucosa (90% survival) ðpT2 into the muscularis propria (+LN metastases possible); ðpT3 subserosa (+ metastases common), 35% survival in LN meta - pT3N1 ðpT4 transperitoneal/invasion into adjacent organ ðDistant metastases present - 8% survival. ð û j0305257 Colorectal carcinoma ûStaging û stage I: T1, T2, no meta û stage II: T3, T4, no meta û stage III: any T, LN meta, no distant meta (M0) û stage IV: any T, any N, M1 j0305257 Colorectal carcinoma adenoCa j0305257 Adenocarcinoma of the colon 12444-11-20x 1Intestinal adenocarcinoma structures 2Normal colonic epithelium 3Muscularis propria 4 1 2 1 1 3 j0305257 Adenocarcinoma of the colon 12461-11-40x 1Adenocarcinoma structures 2Pericolonic fat and fibrous tissue 3 2 1 j0305257 Adenocarcinoma of the colon 12461-11-100x 3 1Perineural invasion of adenocarcinoma 2Peripheral nerve 3Pericolonic fat 4 2 1 j0305257 Adenocarcinoma of the colon 12769-11-40x 1Mucinous adenocarcinoma 1 1 j0305257 Colorectal carcinoma - complications ûstenosis ûobstructive ileus ûhemorrhage (occult!, overt) ûperforation ûpenetration ûstercoral peritonitis j0305257 Peritoneal carcinomatosis widespread metastases in the peritoneum/ omentum karcinoza 40x 1 Adenocarcinoma 2 Adipose tissue of the omentum 2 1 2 j0305257 Appendix - normal apendix norma copy j0305257 Appendix - periappendicitis apendicitis copy j0305257 Appendicitis ûCauses: ?obstruction, stool stagnation→ collapse of the draining veins → ischemia of the wall → bacterial proliferation → inflammation (catarrhal, phlegmonous) ûTrombosis of mesenteriolar veins → ischemic necrosis of the appendiceal wall → secondary bacteria invasion → gangrenous inflammation ûComplications: ðperitonitis ðperiappendiceal abscess ðportal pyemia ðadhesions j0305257 Phlegmonous appendicitis flegm app 20x 1 Sec. lymph. follicle in the submucosa 2 Intraluminal hemorrhage 3 Inflammatory infiltrate 1 2 3 3 3 j0305257 Phlegmonous appendicitis - detail flegm app 100x 1Inflammatory infiltrate 2Inflammatory reaction on the serosa 3Hyperemic subserosa 1 1 2 3 j0305257 parazitární apendikopatie Parasitic appendicitis - Oxyuriasis vermicularis (pinworm) in the lumen j0305257 Neuroendocrine tumors (NETs) ûarise from neuroendocrine cells of the gastro-entero-pancreatic system (GEP-NET) û ûhistologic classification WHO 2010: ð ðNET G1 (carcinoid) ðNET G2 ðNEC G3 large cell or small cell type ðcompound adenoneuroendocrine carcinoma ð j0305257 Neuroendocrine tumors (NET) û û arise from neuroendocrine or precursor cells of the GIT mucosa û û û mostly in the ileum and appendix (80%) û û all NETs (except for a very few) are considered malignant in various grade û j0305257 GEP-NET ûclassification depends on: ðlocation ðtype of the endocrine product û ûgross: ðsmall, round-shaped, flat nodules of yellowish colour, infiltrating the wall to different depth, superficially ulcerated or covered with normal mucosa, sometimes exophytic û û j0305257 GEP-NET ûmicro: ðtrabecular, glandular structures - tubules, palisading or compound structure ðregular cells with clear cytoplasm and round or oval-shaped nucleus; slight nuclear polymorphism ðlow mitotic activity ðchromogranin A in cytoplasm û j0305257 GEP-NET û possible production of various endocrine substances: serotonin, somatostatin, gastrin û serotonin active only locally in intestine → intestinal hypermotility with diarrhea û liver metastases → carcinoid syndrome: û cutaneous „flush“ and cyanosis, nausea and vomiting, astmatic bronchoconstrictive attacks, endocardial fibrosis in right ventricle, hepatomegaly û j0305257 Carcinoid of the appendix karcinoid appendixu 40x 1 Tumor cells 2 Appendiceal mucosa 1 1 2 j0305257 Carcinoid of the appendix detail karcinoid appendixu 100x 1 Tumor cells 2 Appendiceal mucosa 3 Stroma of the tumor 2 1 2 3 j0305257 Carcinoid of the appendix (IHC chromogranin) karcinoid appendixu 100x CHRG j0305257 THANK YOU FOR ATTENTION