Stomach and Colon CA Flashcards by Denisse Tiangco

Cells that secrete mucus in the Cardia

foveolar

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Reduces mucin synthesis by inhibiting cox and prostaglandin or reducing bicarbonate

NSAID

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Neutrophil above basement membrane signifies active inflammation
Intact surface epithelium

Erosion loss of epithelium
Mucosal neutrophilic infiltrate and purulent exudate
Hemorrhage
Layer of necrotic debris, inflamm, granulation, fibrotic scar,

Acute gastritis

Acute erosive hemorrhagic gastritis

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Affects critically ill shock, sepsis, trauma

Sharply demarcated with normal adjacent mucosa

Stress ulcer

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Proximal duodenum assoc with severe burns and trauma
Acidosis lowers intracell pH of mucosal cell
Hypoxia and reduced bf by stress vasoconstriction

Curling ulcer

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Stomach, duodenum, esophagus with intracranial disease
High incidence of perforation
Due to direct stimulation of vagi nuclei causing gastric acid hypersecretion

Cushing’s ulcer

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Round, less than 1 cm, base stained brown black by acid digested RBCs with transmural inflamm and local serositis

Acute peptic ulcer

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Most common cause of chronic gastritis is

Antral gastritis
Pit abscess

Infection with bacillis H pylori

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Most common cause of atrophic gastritis
Less than 10% of cases
Most common form of chronic gastritis without H pylori infection

Typically spares the antrum and includes hypergastrinemia
Characterized by:
antibodies to parietal cells and intrinsic factor
vitamin B12 deficiency
defective gastric acid secretion (achlorhydria)

Autoimmune gastritis

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Manifests as predominantly antral gastritis with high acid production despite hypogastrinemia
Inc risk of ulcer but gastritis limited to antrum

Antral gastritis
Pit abscess

Lymphoid aggregates with germinal centers and abundant subepithelial plasma cells

H pylori associated gastritis

MALT lymphoma

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H pylori virulence

Flagella - for motility
Urease - for ammonia elevating local gastric pH around organism and protecting bacteria from acidic pH of stomach
Adhesins - enhance bacterial adherence to foveolar cells
Toxins - by cytotoxin associated gene A (CagA) in ulcer or cancer

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Chronic antral H pylori may progress to

pangastritis resulting in multifocal atrophic gastritis

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H pylori complications

Atrophic gastritis
Reduced secretion
Intestinal metaplasia
Inc risk of gastric adenoCa
MALT -> lymphoma

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H pylori gastritis preferred eval

antral biopsy

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Less than 10% of gastritis cases

Spares antrum

Induces hypergastrinemia

Autoantibodies to parietal and IF
Reduced serum pepsinogen I level

Antral endocrine cell hyperplasia

Vit B12 deficiency

Defective gastric acid secretion (achlorydia)

Autoimmune gastritis

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T/F: H pylori is not associated with pernicious anemia.

bec parietal and chief cell damage is not as severe as autoimmune gastritis

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Diffuse atrophy of parietal oxyntic cell in body and fundus 
Thinned rug folds lost
Parietal and chief cell loss
Lymphocytic, mac and plasma infiltrate
Intestinal metaplasia

Autoimmune gastritis

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Neutrophil, subepithelial plasma cell
Inc acid production
Normal to dec gastrin
Hyperplastic inflammatory polyp
Antibody to H pylori
Peptic ulcer, adenoCa, lymphoma
Low socioecon status, poverty

H pylori Antrum Gastritis

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Lymphocyte mac
Dec acid
Inc gastrin
Neuroendocrine hyperplasia
Autoantibody to parietal cell HKATpase IF
Atrophy, pernicious anemia, adenoCa, carcinoid
Autoimmune thyroiditis, DM, Graves

Autoimmune gastritis

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PUD is most common in the
Usually solitary less than 0.3cm, shallow but if 0.6 deeper
Round to oval sharply punched out defect
Smooth clean base from peptic digestion

gastric antrum (interface of body and antrum)
first portion of duodenum (4x)

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Primary underlying cause of PUD (2) resulting in imbalance of mucosal defense and damaging forces causing chronic gastritis

NSAID
H pylori 70% assoc but only 5-10% develop ulcers

Also smoking and corticosteroids

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Multiple peptic ulcer in stomach, duodenum, jejunum by uncontrolled gastrin release by tumor

Zollinger-Ellison

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CRF and hyperparathyroidism predispose to peptic ulcerations because

hypercalcemia stimulates gastrin production and inc acid secretion

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Multiple ovoid covered by smooth surface
Irregular cystically dilated foveolar gland
Precancerous in situ lesion:l development correlates with size
Significant inc risk in >1.5cm

gastric Polyp

Dysplasia

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``` Sporadic or FAP but benign inc bec of PPI use from inc gastrin in response to reduced acidity and glandular hyperplasia Nausea, vomiting and epigastric pain occur in body and fundus Multiple cystically dilated glands ```

Fundic gland polyp

10% of all polyps, intestinal columnar M 3x Occurs in chronic gastritis with atrophy and intestinal metaplasia Risk of development of adenocarcinoma is related to size of lesion elevated in >2cm diameter Carcinoma in 30% Dysplastic Most common in

Gastric adenoma antrum

Most common malignancy of stomach 90% Dyspepsia dysphagia nausea Weight loss, anorexia, altered bowel habits, anemia, hemorrhage Common in low socio, multifocal atrophy and intestinal metaplasia Gastric cardia cancer on rise bec of Barrett

Gastric adenoCa

Mutations in gastric ca

CHD1 encoding e-cadherin for intracellular adhesion (familal diffuse type)

Key step in development of diffuse gastric cancer

E cadherin function loss

FAP patients have inc risk for gastric ca bec of mutation of

APC gene | Mutation of b catenin, microsatellite instability

Gastric adenoCa pathogenesis

Gene mutation H pylori bec of chronic gastritis induced IL 1B production and TNF prod EBV

Lauren classification is according to

intestinal | diffuse

Bulky glandular structure similar to esophageal and colonic adenoCa Broad cohesive front either as exophytic mass and ulceration Apical mucin vacuoles abundant mucin Precursor: flat dysplasia and adenoma

Intestinal type gastric adenoca

Infiltrative growth pattern Discohesive cells with large mucin vacuole expanding cytoplasm and pushing nucleus to periphery creating signet ring cell Evoke desmoplastic reaction stiffening the wall causing diffuse rugal flattening Mucin lakes

Diffuse type gastric adenoca

Rigid thickened wall imparting leather appearance on diffuse gastric ca Diffuse rugal thickening

linitis plastica | Assoc with signet ring

Most powerful prognostic factor for gastric cancer

Depth of invasion, extent of nodal and distant metastasis at time of diagnosis

Most common gastric malignancy lymphoma

Indolent extranodal marginal zone B cell lymphoma | MALT

Second most common primary lymphoma of gut

Diffuse large B cell

Arise from neuroendocrine organs and G cells 40% in SI (ileum) also in tracheobronchial and lungs Endocrine hyperplasia, chronic atrophic gastritis, Zollinger-Ellison Best considered to be well-differentiated neuroendocrine carcinomas - arise from the endocrine cells Slow growing small polypoid yellow tan lesions with intense desmoplastic reaction islands, trabeculae, glands, sheets of uniform cells scant, pink, granular cytoplasm round oval stippled nucleus Mitotic marker:

Carcinoid Ki67

High grade neuroendocrine carcinomas display And most common in

Necrosis Jejunum

Most important prognostic factor for carcinoid is foregut midgut hindgut

location rarely metastasize before Lig of Treitz Jejunum and ileum multiple, aggressive greater depth of local invasion inc size and necrosis mitosis Appendix and colorectal, benign ocassionaly metastasize

Most common mesenchymal tumor of abdomen half occuring in stomach

GIST

75-80% | GIST have oncogenic

gain of function mutation of tyrosine kinase c-KIT 8% PDGFRA Arise and share common stem cell with interstitial cells of Cajal (gut pacemaker)

Solitary, well circumscribed fleshy submucosal mass Mets to liver Thin elongated spindle cell or plumper epitheloid cell Spindle Epitheloid

GIST

Most useful marker for GIST

c-KIT 95%

GIST is less aggressive than those

arising fr intestine

GIST tx

Imatinib (tk inhibitor) Also in CML BCR-ABL gene

Reactive lesions assoc with chronic gastritis | Risk of dysplasia correlates with polyp size

Inflammatory and | Hyperplastic polyp

Most common etiologic agent for gastric adenocarcinoma

H pylori

Most common benign neoplastic (dysplastic) polyp gives rise to adenocarcinoma

Adenoma

Non neoplastic polyp

Inflammatory Hamartomatous Hyperplastic

Polyp of solitary rectal ulcer syndrome Rectal bleeding Mucus dc Inflammatory lesion of ANTERIOR rectal wall Impaired relaxation of anorectal sphincter creating sharp angle at rectal shelf Recurrent abrasion, ulceration of rectal mucosa Polypoid mass of inflammed and reactive tissue

Inflammatory polyp

Sporadic or syndromic Disorganized tumor growths of mature cell Rare Mosy common type: Children <5 Located in rectum Rectal bleed, prolapse Juvenile polyposis assoc with inc risk

Hamartomatous polyp Juvenile polyp

Pedunculated smooth reddish less than 3 cm with cystic spaces Dilated glands filled with mucin and inflammatory debris Mucosal hyperplasia, mutation in pathways that regulate cell growth such as TGF B with AD polyposis

Hamartomatous polyp

Rare AD with multiple GI hamartomatous polyp and mucocutaneous hyperpigmentation inc risk of malig Colon, pancreas, breast, lung, ovary etc Intestinal polyp in SI, large pedunculated with lobulated contour Arborizing network of CT smooth ms lamina prop and glands by normal epi

Peutz Jeghers syndrome

Peutz Jeghers is assoc with heterozygous loss of function mutation in gene

LKB1/STK11

Dec epithelial cell turnover, delayed shedding of surface epithelial cell leading to pileup of goblet cell No malignant potential Most common on LEFT COLON Less than 5cm, smooth, nodular, protrusion of mucosa on crests of mucosal fold Multiple in sigmoid and rectum with mature goblet and absroptive cell Delayed shedding leading to crowding creating serrated surface that is morphologic hallmark of these lesions

Hyperplastic polyps

Screening for colon adenoCa

All adults in US undergo colonoscopy starting age 50 If with family hx, screen at least 10 years before youngest age at which relativr was dx

0.3-10cm, pedunculated, sessile with surface resembling velvet or raspberry Epithelial dysplasia with nuclear hyperchromasia, elongation, stratification at surface Epithelium fails to mature as cells migrate out of crypt Pedunculated have slender fibromuscular stalk with prominent blood vessel from submucosa Stalk covered by non neoplastic epi

adenoma of colon

Adenoma types

Tubular - small, pedunculated, small rounded tubular gland Tubulovillous Villous - large, sessile slender

Most common on the RIGHT colon Have malignant potential Overlap features with hyperplastic but lacking dysplasia Serrated architecture throughout full length of glands and CRYPT involvement (vs hyperplastic)

sessile serrated adenoma

Most important characteristic correlating with risk of malignancy

Size 40% larger than 4cm contain foci of cancer High grade dysplasia in individual polyp

AD, appearance of numerous colorectal adenoma by teenage year A count of at least 100 necessary Morphologically indistinguishable from sporadic adenoma

Familial Adenomatous Polyp

FAP is associated with mutations of Colorectal CA in 100% before 30 if untreated Tx

APC gene Prophylactic colectomy At risk for extraintestinal manif ex neoplasia at other site

APC FAP variant

Garnder | Turcot

``` Osteoma FAP Epidermal cyst Desmoid and thyroid tumor Dental abnormality ```

Gardner

Intestinal adenoma FAP Medulloblastoma/CNS Glioblastoma

Turcot syndrome

FAP without APC loss have mutation base excision on repair gene

MUTYH

Familial clustering of cancer Colon Ca: younger and affects RIGHT colon Result from mismatch repair and microsatellite instability

Hereditary Nonpolyposis Colorectal Cancer HNPCC Lynch syndrome

HNPCC involves mutation of

MSH2 | MLH1

Most common malignancy of GI tract

Adenocarcinoma

Cause polyp regression in patients with FAP whom rectum was in place after cole

NSAID | inhibits COX2 in 90%

Events that lead to colon adenocarcinoma formation

1 APC/Beta catenin pathway - classic adenoma sequence | 2 Microsatellite instability pathway

80% of sporadic colon tumors Mutation in APC both must be inactivated Key negative regulator of beta catenin a component of WNT signalling pathway Beta catenin accum due to inh of APC MYC and cyclin D1 activation promoting prolif KRAS mutation TP53 mutation

APC/Beta catenin pathway

DNA mismatch repair deficiency Silent, type II TGFB and Bax BRAF mutation MHL1

Microsatellite instability

Polypoid exophytic extending along wall of large caliber cecum Rarely cause obstruction

Tumors in proximal colon

Annular producing napkin ring constrictions and luminal narrowing

Distal colon ca Tall columnar dysplastic epithelium Strong stromal desmoplastic response - firm consistency Mucin producing - poor prognosis

IDA fatigue weakness

Cecal | Right sided colon ca

Occult bleeding Changes in bowel habits Cramping

Left sided colorectal adenocarcinoma

Two most important prognostic factors in colon ca

Depth of invasion Presence/absence of lymph node metastases Invasion to muscularis prop dec survival

Most common site of metastasis bec of portal drainage

liver

APC/WNT pathway Target: APC Autosomal dominant Tubular, villous, typical adenoCa

FAP 70%

``` DNA mismatch repair Target: MUTYH None or autosomal recessive Sessile serated adenoma Mucinous adenoma ```

FAP <10%

``` DNA mismatch repair Target: MSH2, MLH1 Autosomal dominant Right sided Sessile serated adenoma, mucinous adenoCa ```

Hereditary Nonpolyposis | Lynch syndrome

``` APC/WNT Target: APC No transmission Left sided Tubular, villous, typical adenoCa ```

Sporadic colon ca 80%

``` DNA mismatch repair MSH2, MLH1 No transmission Right sided Sessile, serrated adenoma Mucinous adenoCa ```

Sporadic colon ca 10-15%

``` Germline or Somatic: APC at 5q21 (first hit) Methylation abn: APC/beta catenin Proto-onco mu: KRAS at 12p12 Homozygous loss of cancer supressor: p53, LOH and SMAD2 and 4 Overexpression of COX additional mutations gross alteration ```

APC/Beta-catenin pathway

Germline or somatic: MLH1 MSH2 MSH6 PMS1 PMS2 Alteration of 2nd allele by LOH, mutation or methylation Microsatellite instability mutator phenotype Accumulated mutations: TGFBRII, BAX, BRAF, TCF4, IGFR2

Microsatellite instability

Lifetime risk for appendicitis

Progressive inc in intraluminal pressure with compromised venous outflow 50-80% asso with overt luminal obstruction by fecalith Ischemic injury, stasis, bacterial inflamm Dull granular appearing erythematous surface Mucosal neutrophil and focal superficial ulceration Neutrophilic infiltration of muscularis propria -dx Focal abscess in wall progressing into hemorrhagic ulcer and gangrene rupture and suppurative peritonitis

Acute appendicitis

Most common tumor of appendix

Carcinoid at distal tip

Acute appendicitis clinically may also present like

Appendiceal carcinoma

LKB/STK I Mean age 10-15 years Arborizing polyp on small intestine > colon > stomach Mucocutaenous pigmentation Thyroid, breast, lung, pancreatic and gonadal cancer

Peutz-Jeghers syndrome

``` SMAD4/BMPRI A Mean age <5 Juvenile polyp inc risk of gastric, si, colon and pancreatic adenoCa Pulmonary AVM Digital clubbing ```

Juvenile polyposis

PTEN Hamartomatous polyp, lipoma, ganglioneuroma, inflamm polyp, inc risk of colon ca Benign skin tumors, benign and malignant thyroid, breast lesion Mean age of presentation: <15

Cowden syndrome | Bannayan-Ruvalcaba-Riley

Nonhereditary Mean age: >50 Hamartomatous colon polyps,crypt dilation, edema in nonpolypoid mucosa Nail atrophy, hair loss, abnormal skin, cachexia, anemia

Cronkhite-Canada syndrome

TSC1,TSC2 Mean age: Infancy to adulthood Hamartomatous polyp (rectal) Facial angiofibroma, cortical tuber, renal angiomyolipoma

Tuberous sclerosis

``` Osteoma Desmoida Skin cyst APC, MUTYH 10-15 years ```

Gardner syndrome

CNS tumor Medulloblastoma APC, MUTYH 10-15 years

Turcot syndrome

Occurs when closure of the abdominal musculature is incomplete Abdominal viscera herniate into a ventral membranous SAC

Omphalocoele

Congenital malformation of abdominal wall (ventral wall) Defect of the right umbilical cord insertion All layers of the abdominal wall (from peritoneum to skin)

Gastroschisis | Laparoschisis

Macroglossia Ear lobe creases Omphalocoele

Beckwidth Wiedemann Syndrome

Most common malignancies associated with Beckwidth Wiedemann Syndrome

Nephroblastoma/Wilm’s | Hepatoblastoma

Occurs as a result of failed involution of the vitelline duct which connects the lumen of the developing gut to the yolk sac 2% of the population Within 2 feet 85 cm of the ileocecal valve Approximately 2 inches 5 cm long 2x as common in males as in females Symptomatic by age 2 2 Ectopic tissues: Gastric and Pancreatic tissue 2 Complications: Bleeding and perforation

Meckel’s diverticulum

2% of the population Within 2 feet 85 cm of the ileocecal valve Approximately 2 inches 5 cm long 2x as common in males as in females Symptomatic by age 2 2 Ectopic tissues: Gastric and Pancreatic tissue 2 Complications: Bleeding and perforation

Meckel’s diverticulum

Most often associated with H pylori-induced hyperchlorhydric chronic gastritis Most common in gastric antrum and first portion of duodenum (duodenal bulb)

Peptic ulcer disease

Four times more common in proximal duodenum than stomach Duodenal ulcers usually occur near pyloric valve (duodenal bulb) Involve anterior duodenal wall

Peptic ulcer disease

Sharply punched-out defects Mucosal defect with clean edges Necrotic ulcer base composed of granulation tissue indicate

benigness

Heaped-up ulcer margins

Malignancy

EXCESSIVE Transforming growth factor alpha (TGF-a) 30-60 y/o DIFFUSE Hyperplasia of foveolar epithelium of BODY AND FUNDUS PROTEIN LOSING ENTEROPATHY -> HYPOPROTEINEMIA Weight loss and diarrhea

Menetrier Disease

50 y/o Gastrin secreting tumor called Gastrinoma Most commonly in small intestine and pancreas Hyperplasia of parietal cells (5x increase) Gastrin -> increase mucin production and neuroendocrine cells Symptoms of peptic ulcer: duodenal ulcer Not associated with adenocarcinoma instead neuroendocrine carcinoma

Zollinger-Ellison Syndrome

Stiffening of gastric walls

Desmoplastic reaction | Gastric adenocarcinoma

Metastases to supraclavicular sentinel lymph node Metastases to periumbilical region Metastases to bilateral ovaries Signet ring cells Palpable nodules in the pelvic cul-de-sac

Late signs of Gastric CA Metastases Virchow node Sister Mary Joseph Nodule Krukenberg tumor Blumer’s shelf

Mucosa-associated lymphoid tissue (MALT) or MALTomas Most common site of extranodal lymphomas: GI tract (stomach) BMT/organ transplant recipients

Gastric lymphoma

The most frequent site for EBV-positive B-cell lymphomas

The bowel

Young females Includes gastric GIST, paraganglioma and pulmonary chondroma Most useful marker is c-KIT

Carney triad | GIST

Acute compromise of any major vessel can lead to intestinal infarction Mucosal infarction: muscularis mucosa Mural infarction: mucosa and submucosa Transmural infarction: all three wall layers

Ischemic bowel disease

Most common cause of ischemic bowel disease

Atherosclerosis ``` Other: aortic aneurysm hypercoagulable states OCP use embolization of cardiac vegetation ```

``` Due to acute arterial obstruction Splenic flexure is the site at greatest risk (Griffith’s point) Rectosigmoid junction (Sudeck’s point) ```

Transmural infarction

Characterized by malformed submucosal and mucosal blood vessels Cecum or right colon After the sixth decade of life Accounts for 20% of major episodes of lower intestinal bleeding

Angiodysplasia

Also known as celiac sprue or gluten-sensitive enteropathy Immune-mediated enteropathy triggered by the ingestion of gluten-containing cereals (wheat, rye or barley) Dermatitis herpetiformis Characteristic itchy, blistering skin lesion

Celiac disease

Most common bacterial enteric pathogen Associated with ingestion of improperly cooked chicken Associated with Guillain-Barre syndrome Serum antibodies to C. jejuni lipopolysaccharide cross-react with gangliosides

Campylobacter enterocolitis

Enteric fever Caused by salmonella typhi or paratyphi Gallbladder colonization may be associated with chronic carrier state Enlargement of Peyer’s patches Neutrophilic infiltration of lamina propria

Tyhpoid fever

Caused by Clostridium difficile | Also known as antibiotic-associated colitis or antibiotic-associated diarrhea

Pseudomembranous colitis

Adherent layer of inflammatory cells and debris

Pseudomembranes

Denuded surface epithelium | Mucopurulent exudate forms an eruption reminiscent of a volcano

Pseudomembranous colitis

Caused by the gram-positive actinomycete named Tropheryma whippelii Malabsorptive diarrea due to impaired lymphatic transport

Whipple’s disease

Diarrhea Weight loss Malabsorption

Whipple’s disease

In small intestinal lamina propria | Contain PAS positive, diastase-resistant granules

Distended foamy macrophages | Whipple’s disease

May involve any area of the GI tract | Typically transmural

Crohn’s disease

Severe ulcerating inflammatory disease that is limited to the colon and rectum Extends only into the mucosa and submucosa

Ulcerative colitis

Most common sites involved at presentation are the terminal ileum, ileocecal valve and cecum Characterized by skip lesions Clinical presentation -bloody diarrhea, fever, rectal abscess, small intestinal and colonic ulcers, fistulae

Crohn’s disease

Earliest Crohn diseaeclesion | Multiple lesions often coalesce into elongated, serpentine ulcers

Apthous ulcer

Sparing of interspersed mucosa a result of patchy distribution

Cobblestone appearance | Crohn’s disease

Limited to the colon and rectum Common extra-intestinal manifestations Migratory polyarthritis, ankylosing spondylitis Uveitis, skin lesions Pericholangitis, primary sclerosing cholangitis Associated with increased risk of colon CA Extent of involvement: Pancolitis: entire colon Backwash ileitis: mild mucosal inflammation of the distal ileum

Ulcerative colitis

Acquired pseudo-diverticular outpouchings of the colonic mucosa and submucosa Most common in the sigmoid colon Diverticulae are generally multiple and referred to as diverticulosis

Sigmoid diverticulitis

Increased luminal pressure due to exaggerated peristaltic contractions, with spasmodic sequestration of bowel Small, flask-like outpouchings - alongside taeniae coli Epiploic appendices - masses of surrounding fat

Sigmoid diverticulitis

Stomach and Colon CA Flashcards

(137 cards)