B5.071 GI Cancers: Tubal Gut Flashcards
esophageal cancers
adenocarcinoma
squamous cell carcinoma
stomach cancers
adenocarcinoma
lymphoma (H.pylori)
neuroendocrine tumor (AMAG)
GIST
colon cancers
adenocarcinoma and precursor polyps
general differences between adenocarcinoma and squamous carcinoma in the esophagus
adenocarcinoma: -distal esophagus -arises from Barrett's -more common in US squamous carcinoma: -middle or upper esophagus -NOT associated with Barrett's -more common worldwide
how does Barrett’s contribute to esophageal adenocarcinoma
initiates metaplasia of the squamous epithelium due to repeated injury of reflux
-replacement with columnar epithelium and goblet cells
may develop dysplasia
-low > high > adenocarcinoma
histo appearance of barrett’s
transition between esophageal squamous mucosa and metaplasia with abundant metaplastic goblet cells
low grade barrett’s dysplasia
nuclear stratification and hyperchromasia
longer nuclei migrating up from base of cell
high grade barrett’s dysplasia
architectural irregularities
gland within gland, cribriform structure
treatment of barrett’s with high grade dysplasia
surveillance if single focus
laser ablation, endoscopic resection of mucosa
risk factors for esophageal adenocarcinoma
GERD
tobacco
alcohol
radiation
protective factors against esophageal adenocarcinoma
diets rich in fruits/veggies
H.pylori infection (causes atrophy of stomach, decreased acid secretion
epidemiology of esophageal adenocarcinoma
M:F = 7:1
rapidly increasing incidence in US
>50% of esophageal cancers in US
presentation of esophageal adenocarcinoma
long standing GERD
odynophagia or dysphagia
weight loss, vomiting, hematemesis
location of esophageal adenocarcinoma
distal 1/3 of esophagus
gross appearance of esophageal adenocarcinoma
flat/slightly raise lesion to large, ulcerated mass later
Barrett’s mucosa around mass
histo appearance of esophageal adenocarcinoma
gland formation and mucin production
may have signet ring formation
molecular alterations present in esophageal adenocarcinoma
start to accumulate in Barrett’s and increase in number until adenocarcinoma
early: p53, APC inactivation
later: amplification of ERBB2/HER2
treatment of esophageal adenocarcinoma
if HER2 amplification - trastuzamab
chemo/radiation
surgical resection (esophagectomy)
prognosis of esophageal adenocarcinoma
early: 80% survival at 5 years
later: less than 25% survival at 5 years
risk factors for esophageal squamous cell carcinoma
smoking alcohol esophageal injury achalasia consumption of very hot beverages lower socioeconomic background
epidemiology of squamous cell carcinoma
more common in Iran, China, Hong Kong, Brazil, South Africa
precursor lesions associated with squamous cell carcinoma
squamous dysplasia
plaque-like thickening
location of squamous cell carcinoma
mid esophagus (50-60%)
distal (30%)
upper (10-20%)
clinical presentation of squamous cell carcinoma
dysphagia, odynophagia, obstruction
weight loss
no heartburn usually
gross presentation of squamous cell carcinoma
mass like lesion, may protrude into lumen and ulcerate
may infiltrate and cause diffuse thickening
histo presentation of squamous cell carcinoma
dysplastic/atypical squamous epithelium invading into submucosa or deeper
variable sized nests of tumor cells with epithelioid cells, ample eosinophilic cytoplasm, keratinization (pink pearls)
low grade dysplasia of squamous cell carcinoma
proliferation of neoplastic cells involving about 1/3 to 1/2 of the thickness of the epithelium
high grade dysplasia of squamous cell carcinoma
dysplastic cells extend to the surface of the epithelium and are associated with significant loss of surface maturation
cellular appearance of dysplasia of squamous cell carcinoma
increased nuclear to cytoplasmic ratio marked hyperchromatic nuclei loss of polarity overlapping pleomorphic
treatment of squamous cell carcinoma
chemotherapy/radiation
surgery
prognosis of squamous cell carcinoma
early: 75% at 5 years
late: less than 20% at 5 years
risk factors for stomach adenocarcinoma
chronic gastritis (H.pylori) inherited disorders (FAP, hereditary diffuse gastric cancer)
epidemiology of stomach adenocarcinoma
more common in japan, chile, costa rica, eastern Europe
incidence has been decreasing in US, <2.5% of cancer deaths
presentation of stomach adenocarcinoma
often asymptomatic or with vague symptoms similar to chronic gastritis and peptic ulcer disease
-dyspepsia, dysphagia, nausea
weight loss
anorexia
early satiety at later stages
metastasis often present at time of diagnosis
precursor lesions associated with stomach adenocarcinoma
intestinal metaplasia
gastric adenoma/dysplasia
2 types of stomach adenocarcinoma
intestinal type
diffuse type
gross appearance of intestinal type stomach adenocarcinoma
mass lesion, often ulcerated
microscopic appearance of intestinal type stomach adenocarcinoma
infiltrating atypical glands with mucin production
associations with intestinal type stomach adenocarcinoma
intestinal metaplasia
FAP
h. pylori
gross appearance of diffuse type stomach adenocarcinoma
diffuse thickening (linitis plastic)
whole stomach wall involved
loses normal folding pattern, looks shrunken
microscopic appearance of diffuse type stomach adenocarcinoma
sheets of cells
sometimes signet ring (prominent intracytoplasmic mucin droplet with enlarged eccentrically located, flattened nucleus)
associations with diffuse type stomach adenocarcinoma
mutations in CDH1 (e-cadherin)
patients also have risk of lobular breast cancer
molecular alterations in stomach adenocarcinoma
TP53 in 40% of all
may display microsatellite instability (MSI)
ERBB2 (HER2) in intestinal type
CDH1 lost in most diffuse type
treatment of stomach adenocarcinoma
resection
chemo (trastusamab for HER2)
prognosis of stomach adenocarcinoma
early: 90% 5 year survival
late/advanced: 20% 5 year survival
characterize the occurrence of stomach lymphoma
extranodal lymphomas can occur anywhere GI tract is a common site primary gastric lymphomas are 5% of gastric malignancy -marginal zone B cell lymphoma -called MALTomas
risk factors for stomach lymphoma
chronic inflammation
H. pylori infection (eradication resolved lymphoma if at an early stage)
presentation/symptoms of stomach lymphoma
dyspepsia
epigastric pain
hematemesis
melena
gross appearance of stomach lymphoma
thickening of wall of stomach
nodular mucosa
microscopic appearance of stomach lymphoma
diffuse of lymphocytes
lymphocytes infiltrate the glandular epithelium
comprised of B lymphocytes
treatment of stomach lymphoma
treat H.pylori if present
chemo
prognosis of stomach lymphoma
90% 5 year survival
risk factors for stomach carcinoid tumor
MEN-I
autoimmune atrophic gastritis (AMAG)
presentation of stomach carcinoid tumor
if functional: zollinger-ellison syndrome, acid hypersecretion
carcinoid syndrome in < 10%
symptoms of carcinoid syndrome
cutaneous flushing sweating bronchospasm abdominal pain diarrhea
gross appearance of stomach carcinoid tumor
mass like lesion or nodule
microscopic appearance of stomach carcinoid tumor
similar to pancreatic NET
many patterns of growth: nests, trabeculae (cords), solid
cells are uniform, moderate cytoplasm, stippled, or salt and pepper chromatin
treatment of stomach carcinoid tumor
resection
prognosis of stomach carcinoid tumor
generally good (especially when associated with AMAG), considered cured after resection sporadic tumors may be more aggressive
characterize a gastrointestinal stromal tumor (GIST)
most common mesenchymal tumor of the abdomen, more than half in the stomach
arise from interstitial cells of Cajal within the muscularis propria
risk factors for GIST
NF1
presentation of GIST
asymptomatic when small
symptoms due to mass effects when large, may ulcerate causing bleeding
molecular characteristics of GIST
most (75-80%) have activation mutations in KIT gene
some (8%) have activating mutations in PDGFRA
treatment with imatinib works in tumors with mutations in these genes
gross appearance of GIST
solid, well circumscribed mass with pink-tan fleshy cute surface in the wall of the stomach
centered on muscularis propria, but may extend to involve mucosa
microscopic appearance of GIST
spindled cells more common, but epithelioid also possible
prominent perinuclear vacuoles (artifact of fixation)
immunohistochemical stains for KIT and DOG1 usually positive
treatment of GIST
resection
imatinib for unresectable, metastatic, or recurrent GISTs with KIT of PDGFRA mutations
prognosis of GIST
depends on location, size, and mitotic activity
bigger and more mitotic activity = worse prognosis
epidemiology of colon adenocarcinoma
3rd most common cancer in US
2nd leading cause of cancer deaths in US
presentation of colon adenocarcinoma
no signs/symptoms early
advanced left sided carcinomas may present with change in bowel habits, abdominal distention, hematochezia
advanced right sided carcinomas: fatigue, weight loss, anemia
risk factors for colon adenocarcinoma
fam fistory inactivity IBD obesity red meat smoking alcohol
protective factors against colon adenocarcinoma
high veggie consumption
oral contraceptive use
estrogen replacement
multivitamin w folic acid
prevention of colon adenocarcinoma
surveillance important for prevention
start at age 50; earlier if positive family history
every 10 years, more often if precursor lesions found
2 pathways for molecular pathogenesis of colon adenocarcinoma
APC/ beta catenin pathway
MSI pathway
APC/beta catenin pathway
classic adenoma > carcinoma sequence
precursor lesion often the tubular adenoma
more commonly left sided
MSI pathways
deficiency in mismatch repair proteins
precursor lesions often the sessile serrated adenoma
do not respond as well to traditional chemo
more commonly right sided
important mutations in colon adenocarcinoma
KRAS, NRAS, and BRAF
if mutated, less/no response to anti-EGFR therapies
familial adenosis polyposis
germline APC mutation
many polyps which are tubular adenomas
follows traditional APC pathways
often have cancer at early age
lynch syndrome/HNPCC (hereditary non-polyposis colorectal cancer)
patients do NOT have multiple polyps
cancer at an early age
follow MSI pathway (germline mutations in mismatch repair proteins)
types of colon polyps
tubular adenoma
sessile serrated adenoma
hyperplastic polyp
tubular adenoma
precursor to adenocarcinoma via APC/beta catenin pathway
low grade dysplasia
microscopic shows tubular architecture with low grade dysplasia/cytologic atypia
sessile serrated adenoma
precursor to adenocarcinoma via MSA pathway
microscopic shows serrated polyp with widened base
lesions without atypia thought to have similar chance to progress as tubular adenoma; increased risk with cytologic atypia
hyperplastic polyp
not a precursor to adenocarcinoma
serrated polyp without dilation at the base
histo of tubular adenoma
smooth surface
rounded glands
active inflammation occasionally present in adenomas causing crypt dilation and rupture
histo of villous adenoma
long, slender projections that are reminiscent of small intestinal villi
histo of dysplastic epithelial cells
increased N:C ratio
hyperchromatic
elongated nuclei
nuclear pseudo stratification
histo of sessile serrated adenoma
goblet cells without features of dysplasia
extension of the neoplastic process to the crypts, resulting in lateral growth
histo of hyperplastic polyp
irregular tufting of epithelial cells due to epithelial overcrowding
serrated architecture when crypts are cut in cross section
gross appearance of colon adenocarcinoma
exophytic mass
diffuse, circumferential thickening
microscopic appearance of colon adenocarcinoma
gland formation, mucin production
invasive islands of atypical glands
central necrosis
may be poorly differentiated or have signet ring features
treatment of colon adenocarcinoma
resection
possible chemo:
5-FU for non MSI tumors
cetuximab (anti-EGFR) for tumors without KRAS, NRAS, or BRAF
prognosis of colon adenocarcinoma
based on stage
overall 5 year survival (65%)
