Stomach and Colon CA Flashcards
Cells that secrete mucus in the Cardia
foveolar
Reduces mucin synthesis by inhibiting cox and prostaglandin or reducing bicarbonate
NSAID
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
Affects critically ill shock, sepsis, trauma
Sharply demarcated with normal adjacent mucosa
Stress ulcer
Proximal duodenum assoc with severe burns and trauma
Acidosis lowers intracell pH of mucosal cell
Hypoxia and reduced bf by stress vasoconstriction
Curling ulcer
Stomach, duodenum, esophagus with intracranial disease
High incidence of perforation
Due to direct stimulation of vagi nuclei causing gastric acid hypersecretion
Cushing’s ulcer
Round, less than 1 cm, base stained brown black by acid digested RBCs with transmural inflamm and local serositis
Acute peptic ulcer
Most common cause of chronic gastritis is
Antral gastritis
Pit abscess
Infection with bacillis H pylori
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
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
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
Chronic antral H pylori may progress to
pangastritis resulting in multifocal atrophic gastritis
H pylori complications
Atrophic gastritis Reduced secretion Intestinal metaplasia Inc risk of gastric adenoCa MALT -> lymphoma
H pylori gastritis preferred eval
antral biopsy
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
T/F: H pylori is not associated with pernicious anemia.
T
bec parietal and chief cell damage is not as severe as autoimmune gastritis
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
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
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
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)
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
Multiple peptic ulcer in stomach, duodenum, jejunum by uncontrolled gastrin release by tumor
Zollinger-Ellison
CRF and hyperparathyroidism predispose to peptic ulcerations because
hypercalcemia stimulates gastrin production and inc acid secretion
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
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
7%
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
