GI Pathology Flashcards

Question

Gastric Lymphoma: most common type, classification, MALToma features and associations, histology

Answer 1

5-10% of malignant neoplasms of stomach - most common extra-nodal lymphoma Mostly non-Hodgkin B cell type - associated with HP or EBV infection Classification: - low grade = MALToma, related to HP - high grade = transformation from MALToma to diffuse large B cell lymphoma MALToma is the commonest gastric non-Hodgkin lymphoma (extra nodal marginal zone lymphoma of MALT) - accounts for >50% cases - strong association with HP infection (eradication of HP treats 70% cases) - "homing" = tend to home back to stomach and presents at early stage (Histology:) - expansile lymphoid infiltrate in lamina propria - lymphoepithelial lesions characterised by destruction and infiltration of glandular structure by lymphoid infiltrate

Answer 2

- commonest GI mesenchymal tumour accounting for 0.2% of GI malignancy - 40-70 males Site: stomach (50-70%) > small intestine > colon > others Pathogenesis: - originate from interstitial cells of Cajal in muscularis propria - activation mutation of c-KIT/CD117 (75-85%) or PDGRFA (10%) Pathology: - IHC of c-KIT/CD117 (diagnostic marker) - tumour cells arranged in fascicles and exhibit bland elongated nuclei (spindle cells) or plumper epithelioid cells - solitary well circumscribed mass Primary treatment is complete resection Imatinib (TKI) therapy for life in unresectable or metastatic tumour (usually >10cm)

Answer 3

Neuroendocrine cell tumour (0.3% of gastric neoplasms) derived from APUD cells of neural crest origin - 75% in GI tract, 25% in lung 3 types in stomach: - Type I - associated with autoimmune chronic atrophic gastritis (decreased acid --> increase gastrin --> G cells hyperplasia) - Type II - MEN1 and Zollinger-Ellison syndrome - Type III - sporadic Carcinoid syndrome: flushing, diarrhoea, SOB, wheezing, tachycardia due to 5HT secretion -- implies liver metastasis Pathology: - uniform round cells with centrally located stippled nuclei and scant eosinophilic granular cytoplasm in organoid pattern - small polypoid, yellow/tan appearance - IHC of neuroendocrine markers e.g. synaptophysin, chromogranin High grade NET are called NEC and resemble small cell carcinoma of lung --> in GI tract, most common at jejunum Prognosis of NET: - Grading - Ki67 IHC stain for proliferation - Location - - foregut --> rarely metastasise and cured by resection - midgut --> metastatise, multiple and aggressive -- MC small bowel tumour - hindgut --> benign course

Answer 4

``` Ischaemia = insufficient blood supply (Infarction = necrosis due to ischaemia) ``` Pathogenesis: - hypoxic injury phase - little damage; epithelial cells resistant to transient hypoxia - reperfusion injury phase - increase O2 = increase ROS; increase WBC and complements = increase inflammation Areas most prone to damage - watershed zones -- end of arterial supplies - -> splenic flexure (Griffith's point) - SMA and IMA - -> sigmoid colon (Sudeck's point) - IMA and hypogastric arteries - superficial portion of mucosa (epithelial lining of villi or crypt) --> farthest away from blood supply ``` Aetiology: Local circulation problems - Luminal BLOCK --> arterial embolism (MC; 50% cases) e.g. AF; SMA most vulnerable as greatest velocity of flow and most acute angle off aorta --> thrombosis (arterial or venous) ``` - Mural NARROWING - -> atherosclerosis - -> vasoconstriction (secondary to shock, vasoconstrictors) - -> vasculitis - Extramural COMPRESSION - -> adjacent mass lesion - -> volvulus, hernia Systemic circulation problems - shock (systemic hypoperfusion leading to insufficient blood supply to vital organs) - -> recall 5 types of shock and effects in frank-starling law BP = CO x TPR (CO = SV x HR where SV dependent on contractility and VR)

Answer 5

``` Mucosal = only mucosal layer Mural = mucosal + submucosal layers ``` - -> both due to systemic hypoperfusion (shock), localised anatomical defects - -> manifests as abdominal pain, melena, abdominal distension - -> progress to transmural if not restored - -> pathology: mucosal necrosis and submucosal oedema Transmural = all layers - -> due to acute occlusion of major mesenteric artery - -> manifests as sudden onset severe pain, bloody diarrhoea - -> perforation, sepsis and shock if untreated - high mortality >50% Pathology: - atrophy or sloughing of surface epithelium, crypts may be hyper proliferative

Answer 6

= variceal dilations of anal and perianal venous plexuses (collateral vessels connecting portocaval systems formed in response to venous hypertension) Common GI lesion affecting 5% of population Risk factors: - persistent elevated venous pressure from chronic constipation - pregnancy - portal HT (rare) Manifests as rectal bleeding, pruritus, prolapse or acute pain (thrombosed haemorrhoids) Classified into internal and external - Internal - -> above dentate/pectinate line -- NO PAIN - -> further divided into grade 1 (no prolapse), 2 (prolapse can be reduced spontaneously), 3 (prolapse can be reduced manually), 4 (irreducible) - External - -> below dentate line -- PAIN (if thrombosed) Pathology: - thin-walled, dilated submucosal vessels beneath anal or rectal mucosa - may have focal mucosal erosion - squamous epithelium for external; columnar epithelium for internal

Answer 7

= vascular malformation (AVM) characterised by tortuous dilation of submucosal and mucosal veins (+ venules and capillaries) uncommon, <1% population but one of the commonest causes of LGIB (20-40% cases) Manifests as recurrent self-limiting bleeding (but up to 15% massive GI bleeding) Location - majority at cecum and ascending colon (80%) Pathogenesis uncertain - mechanical: intermittent occlusion of penetrating veins during peristalsis --> lead to dilation and loss of precapillary sphincter function --> AVM) - degenerative vascular changes - sometimes associated with ESRD

Answer 8

Caused by bacteria (Vibrio, gram negatives, C. difficile), virus. (rotavirus, norwalk, enterovirus, CMV) or parasites (nematodes, custodies, hookworms etc.) - enterotoxigenic E.coli common - agents vary with host factors e.g. paediatric diarrhoea --> enteric viruses Presents as diarrhoea, sometimes with ulceration and inflammation of intestine Specific diagnosis by stool culture Intestinal tuberculosis - pathology: necrotising granuloma (necrotic centre, epithelioid histiocytes, langhans giant cells) - granulomas can be present in all layers of bowel wall and cause transmural disease (cause strictures, fibrosis, perforation) - Dx: ZN stain, TB culture, TB PCR Pseudomembranous colitis - due to toxins of C.difficile (disruption of normal colonic bacteria allow C.diff overgrowth) --> detection of toxin for Dx - org. particularly prevalent in hospitals - water diarrhoea, abdominal cramping, fecal leukocytes - pathology: layer of inflammatory cells (neutrophils) and debris overlying sites of mucosal injury; damaged crypts distended by mucopurulent exudate that "erupts" - grossly seen as yellow plaques over bowel mucosa - treatment: antibiotics (metronidazole, vancomycin), fecal microbiota transplantation Many bacterial infections have similar histology (acute self-limited colitis) - intraepithelial neutrophil infiltrates, cryptitis (neutrophil infiltration of crypts), crypt abscess - preservation of crypt architecture (distinguish for chronic inflammation)

Answer 9

Increasing incidence in HK - normally present in young adults Pathogenesis uncertain (idiopathic) but proposed ones include: - NOD2 mutation (not in HK) - aberrant host mucosal immune response (Th1/2/17 cells) -- treatment of IBD with immunomodulation or immunosuppression - altered gut microbiota - defective tight junctions of epithelium Risk factors: - smoking --> risk for CD but protective for UC Crohn's Disease - 1/100000 - abdominal pain and diarrhoea (+/- mucus if colon/ anus involved), fever - affects whole GIT, most commonly at cecum and ileum - SKIP LESIONS - TRANSMURAL inflammation --> thick wall - APHTHOUS ULCERS progress and coalesce --> deep linear ulcers and fissures --> COBBLESTONE appearance (coarse textured) - mural fibrosis, strictures, serositis Ulcerative Colitis - 2/100000 - abdominal pain and blood mucoid diarrhoea - affects RECTUM +/- colon - continuous lesions - MURAL inflammation --> thin wall - superficial broad based ulcers and no fissures - no fibrosis, strictures or serositis - isolated islands of regenerating mucosa bulge into lumen --> pseudo polyps

Answer 10

Active chronic inflammation - ACTIVITY shown by erosion, ulceration, cryptitis (neutrophil infiltrate epithelial cells), crypt abscess (neutrophils within crypt lumen) - CHRONICITY with glandular distortion, branching (evidence of regeneration), atrophy (and fibrosis), epithelial metaplasia (pseudo pyloric; paneth cell metaplasia in left colon) CD --> NON-CASEATING GRANULOMA Complications of CD and UC - CD --> MALABSORPTION (e.g. B12 deficiency), strictures (esp terminal ileum), fistula, perforation - UC --> IDA, toxic megacolon (infl mediators disturb neuromuscular function and damage muscularis propria) Both have increased malignant risk and dysplasia (UC>CD) - risk increases with duration (>8-10 years), extent (pancolitis > proctitis), activity (frequent inflammation) - need regular endoscopic surveillance (higher risk of dysplasia if have PSC so need earlier check) Extracolonic manifestations: - eye: uveitis - joints: ankylosing spondylitis, enteropathic arthritis - legs: erythema nodusum, pigmentation - liver: PSC (more in UC) - clubbing

Answer 11

Diverticulum = blind pouch protruding from luminal organ - True = congenital out pouching of all layers of bowel wall e.g. Meckel's diverticulum - False = herniation of mucosa and submucosa through muscularis propria into subserosal region e.g. diverticulosis coli - diverticular disease = symptomatic diverticula - diverticulitis = infection of diverticulum Pathogenesis: - outpouching at focal weakness of wall where arterial vasa recta/ nerves penetrate inner circular muscle coat to create discontinuities in the muscle wall - increased luminal pressure e.g. constipation, low fibre diet Pathology: - thin wall composed of flattened mucosa, compressed submucosa and attenuated muscularis propria Presentation: - mostly middle aged/ elderly (80% asymptomatic) - at sigmoid colon (smaller luminal diameter and increased pressure) - vague abdominal distension/pain Complications: - bleeding from vasa recta (MC cause of LGIB), diverticulitis (due to stasis of contents), perforation and peritonitis/pericolic abscess, stricture (IO), fistula

Answer 12

Misnomer - can be multiple, non-ulcerated, outside rectum (at sigmoid colon) 1/100000 - affecting all ages Presents as rectal bleed, tenesmus, mucosal discharge MIMICS CA RECTUM GROSSLY

Answer 13

= lesion which projects into lumen of bowel - sigmoid colon is the most common site for GI polyps (also diverticula and CA) Classification of polyps: - pedunculated vs sessile - neoplastic vs non-neoplastic Non-neoplastic: - hamartomatous, inflammatory and hyperplastic Neoplastic: - adenoma, sessile serrated adenoma, traditional serrated adenoma, carcinoma - all are precursors or pre-malignant lesions for colonic CA Serrated polyps = histological appearance of sessile serrated adenoma, traditional serrated adenoma and hyper plastic polyp

Answer 14

Hamartomatous polyp = disorganised overgrowth of tissue indigenous to the site - mostly sporadic; may be syndromic in familial polyposis syndrome --> need to screen family members - have extraintestinal manifestations - subtypes: juvenile/ peutz-jeghers Juvenile polyps: (MC type) - children <5 - most common at rectum, with rectal bleed and prolapse through sphincter - syndromic: 3-100 polyps; higher risk of adenoCA - histology: <3cm, CYSTIC DILATION of glandular structures (filled with mucin and inflammatory debris) in inflamed stroma Peutz-Jeghers polyps - rare AD disorder (LKB1/STK11 gene) - most common at jejunum/ileum, then colon and stomach - over entire GI tract - mucosal pigmentation of buccal mucosa, lips - small malignant potential but increases risk of CA colon, breast, ovary, pancreas - histology: network of SMOOTH MUSCLE CORES extend into polyp and surrounding normal looking glands ("Christmas tree")

Answer 15

= mucosal overgrowth secondary to chronic recurrent mucosal injury and regeneration - associated with IBD, solitary rectal ulcer and other chronic colitis - clinical triad of rectal bleed, mucus discharge, inflammatory lesion of anterior rectal wall - histology: markedly inflammed stroma and regenerating glands, inflammed granulation tissue

Answer 16

Benign neoplasm, well known PRECURSOR of colorectal adenoCA - incidence increases with age - characterised by EPITHELIAL DYSPLASIA Classified by architecture and dysplasia - tubular MC (>75% tubular glands): MC in sigmoid colon, small pedunculated polyps composed to small, rounded or tubular glands - tubulovillous: cauliflower like, mixture - villous (>75% villous): least common, finger-like projection with highly dysplastic cells, large, sessile, covered but slender villi, secrete protein and K rich mucus, more frequent foci of invasion, larger sessile - low grade dysplasia - simple architecture, mild atypia (preserved nuclear polarity, cigar-shaped nuclei) - high grade dysplasia - complex architecture, marked atypia (loss of polarity, distinct nucleoli, round vesicular nuclei) --> progress to CA if untreated Advanced adenoma (higher malignant potential) = SIZE MOST IMPORTANT - >1cm (foci of cancer 40% if >4cm), presence of villous component, high grade dysplasia

Answer 17

= serrated (sawtooth) architecture of epithelial component Hyperplastic polyp - MC polyp in adult, 75% of hyperplastic polyps - decreased turnover of epithelium and delayed shedding leading to "pile up" of goblet cells - NON-MALIGNANT - common site: left colon (sigmoid) - morphology: <5mm, sessile, star shaped lumina/ serrated architecture at SURFACE Sessile serrated adenoma - 25% - PRE-MALIGNANT - right colon - >5mm (larger than hyperplastic), serrated architecture throughout the full length of glands, including CRYPT BASE -- important to distinguish from hyperplastic Traditional serrated adenoma - 1% - PRE-MALIGNANT - left colon - larger than hyperplastic, sessile/pedunculated

Answer 18

<1% of CRC --> typical adenoCA - AD mutation in APC gene (TSG) Phenotype: >100 adenomas (usually >1000), 100% risk of CRC by 30 years old Histology: tubular, villous adenoma Extracolonic manifestations: multiple gastric fundic polyps, increased risk of CA thyroid, GB and adrenals Diagnosis: colonoscopy >100 polyps Screening: flexible sigmoidoscopy Q1y from puberty to 50yrs old Treatment: prophylactic colectomy (but still have risk of extracolonic manifestations), NASID/COX2 inhibitor to decrease polyp burden Other syndromes with FAP variants: - attenuated FAP = <100 polyps, later onset, 10% with MYH gene mutation - Gardner syndrome = FAP + extracolonic manifestations (sebaceous/epidermoid cyst, osteoma, desmoid tumour - SOD) - Turcot syndrome = FAP + CNS tumours (medulloblastoma and glioblastoma)

Answer 19

All AD Peutz-Jeghers syndrome - STK11 gene (multiple PJ polyps, mucosal pigmentation, risk of CA in breast, pancreas, ovaries, lung, uterus) Cowden syndrome - PTEN gene (multiple hamartomatous polyps, oral papillomas, risk of CA breast and thyroid) Cronk-hite canada syndrome - non hereditary (multiple hamartomatous polyps, nail atrophy, skin pigmentation, alopecia) Juvenile polyposis syndrome - SMAD4 gene (50-100 juvenile polyps, increased risk of gastric intestinal and pancreatic adenoCA) Serrated polyposis syndrome - non hereditary (>20 serrated polyps throughout colon/ serrated polyps with +ve hx of serrated polyposis)

Answer 20

commonest hereditary disease associated with colorectal cancer -- 5-7% CRC - AD mutation in MMR (mismatch repair) genes (MLH1, MSH2) leading to micro satellite instability - microsatellite = repetitive, non-coding short DNA sequence --> particularly prone to replication errors - phenotype: multiple polyps but not polyposis (excessive); predominantly right-sided - 80% lifetime risk of CRC Histology: sessile serrated adenoma Extracolonic manifestations: increased risk of CA endometrium, ovary, small bowel, stomach, bile duct etc. Diagnosis: genetic analysis of DNA MMR genes Screening: - clinical - Amsterdam criteria (>3 relatives with CRC or Lynch associated CA; >2 successive generations, >1 tumour before 50 yrs old) - pathological - IHC of MMR protein in nucleus (MLH1-PMS2; MSH2-MSH6 --> further genetic test to see which gene in the pair is involved once there is loss of nuclear IHC staining), detection of micro satellite instability (Q1y) Treatment: genetic counselling, consider prophylactic colectomy/hysterectomy

Answer 21

Most common cancer and 2nd in mortality in HK - 85-90% sporadic, 10% familial syndromes Risk factors: - lifestyle - high fat and refined carb diet, low fibres and vitamins A/C/E, smoking, alcohol, obesity - IBD - UC>CD - genetics: Lynch syndrome, polyposis syndrome Prolonged aspirin or NSAID use is a protective factor Histology: adenocarcinoma (recall classical description of a tumour - architecturally... cytologically...); tall columnar epithelial cells; mucinous histology (signet ring cells) associated with poor prognosis Morphology: - distributed equally along entire length of colon (but rectosigmoid>ascending colon and ceum>transverse colon>descending colon) - right sided tumours grow as POLYPOID EXOPHYTIC masses that extend along on wall --> rarely cause obstruction (large caliber lumen), tend to bleed - left sided tumours are ANNULAR/CIRCUMFERENTIAL and produce "napkin ring" constrictions and luminal narrowing --> tend to obstruct -- pencil stool, tenesmus, IO Presentation: - general: change of bowel habit, rectal bleeding, anemia, abdominal pain, tenesmus, weight loss - right sided tumour --> fatigue, weakness due to Fe def anemia - left sided tumour --> obstructive symptoms (altered bowel habit), occult bleed - metastasis to distant organs - esp liver due to drainage of venous return via portal venous system; also lungs

Answer 22

Many different molecular pathways: Chromosomal Instability (CIN), Microsatellite Instability (MSI), CpG island methylation phenotype (CIMP) Carcinogenesis: - stepwise accumulation of genetic and epigenetic abnormalities - Classical adenoma-carcinoma sequence in chromosomal instability - 80% of sporadic CRC - -- APC mutation (both inactivated) --> accumulation of beta catenin (promote proliferation) --> KRAS mutation, DNA hypomethylation --> SMAD2/4 and TP53 mutations --> adenoCA --> PRL3 activation --> metastasis - -- tubular/villous adenoma --> typical adenoCA - -- predominantly left-sided - -- FAP (no predominant side) - microsatellite instability pathway - 10-15% sporadic CRC - -- DNA MMR gene deficiency - MLH1 and MSH2 mutations --> accumulation of sequences at coding or promoter regions of genes involved in regulation of cell growth e.g. pro-apoptotic BAX, type II TGF-beta receptor (inhibits cell cycle) --> adenoCA - -- serrated pathway: sessile serrated adenoma --> mucinous adenoCA - -- predominantly right sided - -- Lynch (genetic testing using IHC of DNA MMR genes) - CIMP (activation of BRAF oncogene) - serrated pathway

Answer 23

Grading: G1-G3 (well - moderate - poorly differentiated) Staging: MOST IMPORTANT PROGNOSTIC FACTOR - depth of invasion and metastasis - AJCC TNM staging Tis = CIS (intraepithelial/ invade lamina propria) - 100% 5 year survival T1 = invade submucosa - 95% survival T2 = invade muscularis propria - 70-90% survival T3 = invade subserosa/ pericolic tissues T4 = perforate visceral peritoneum or other organs - Dukes staging (A = invade into but not through bowel wall, B = invade through bowel wall but no LN, C = spread to LN, D = distant metastasis N0-N2 (N0 = stage IIC) M1 (stage IV, <15% survival)

Answer 24

EGFR over expression in 80% patients with metastasis --> potential for anti-EGFR monoclonal Ab treatment --> need to check for downstream KRAS and NRAS mutations (45% patients) which renders patient unresponsive to anti-EGFR therapy (negative predictor) (c.f. EGFR mutation in lung ADC used TKI therapy and screens for patients with mutation) Serum CEA - detect recurrence, monitor response Screening: - fecal occult blood test - not sensitive/specific (can't differentiate Hb or myoglobin) - fecal immunochemical test: test for Hb - fecal DNA test - more sensitive - colonscopy - most sensitive Recommendations: start at 50, Q10yrs if normal, Q3-5yrs if polyps removed

Answer 25

Refer to flashcards for stomach

Answer 26

Appendix is normal true diverticulum of cecum Acute appendicitis MC in young adults - M>F - diagnosis can be difficult to establish pre-operatively - may be confused with mesenteric lymphadenitis, acute salpingitis, meckel diverticulitis, ectopic pregnancy Pathogenesis: - progressive increase in intraluminal pressure that compromises venous outflow --> ischemic injury and stasis of luminal contents --> bacterial proliferation and inflammation Usually due to overt lumen obstruction by small stone-like mass of stool (fecalith); less commonly by gallstone, tumour, mass of worms Pathology: - subserosal vessel congestion, perivascular neutrophilic infiltrate in all layers of wall - diagnosis requires neutrophilic infiltration of muscular propria - severe cases --> focal abscesses (acute suppurative appendicitis) --> haemorrhagic ulceration and gangrenous necrosis (acute gangrenous appendicitis) Grossly: inflammatory reaction causes serosa to become dull, granular appearing erythematous Presentation: (often not distinctive) - periumbilical pain that localised to RLQ - nausea, vomiting, low grade fever - mildly elevated WBC - McBurney's sign (deep tenderness at 2/3 distance from umbilicus to right ASIS)

Answer 27

Carcinoid is most common - incidental finding - distal tip of appendix -- solid bulbous swelling 2-3 cm - nodal metastasis infrequent Non-mucin-producing adenoCA/ conventional adenoma - obstruct and enlarge appendix mimicking acute appendicitis Mucocele (dilated appendix filled with mucin) - may be due to obstruction - may be due to mucinous cystadenoCA -- intraperitoneal seeding and spread --> may lead to pseudomyxoma peritonei in most advanced cases (abdomen filled with semi-solid mucin)

Answer 28

Hernia, intestinal adhesions, intussusception and volvulus account for 80% cases; remaining 20% by tumours/ infarction Present as - pain, distention, vomiting, constipation Intussusception: segment of intestine (constricted by peristalsis) telescopes into immediately distal segment -- pulls mesentery along - may progress to IO, compressed mesenteric vessels and infarction - MC case of IO in children <2 yrs old - no underlying anatomic defect Hirschprung Disease: congenital defect of colonic innervation - aka congenital aganglionic megacolon -- always affects the colon - neonates with failure to pass meconium in immediate postnatal period followed by obstructive constipation - may cause enterocolitis, electrolyte disturbances, perforation, peritonitis Abdominal Hernia: defect in wall of peritoneal cavity permitting protrusion of serosa-lined pouch of peritoneum - inguinal, femoral, umbilical, surgical - SB loops most common - pressure at neck may impair venous drainage --> stasis and edema - permanent entrapment = incarceration - arterial and venous compromising over time = strangulation

GI Pathology Flashcards

(52 cards)