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159 Cards in this Set

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COLON - LEE - FRIDAY FEB 16
NON-NEOPLASTIC POLYPS
what types of non-neoplastic polyps exist (5)?
1) hyperplastic polyps; 2) juvenile polyps; 3) hamartomatous polyps; 4) inflammatory polyps; 5) lymphoid polyps
what are the most common colonic polyps, and what % does it account for?
hyperplastic polyps (90% of epithelial polyps)
at what age are they most common?
sixth and seventh decades
what symptoms do hyperplastic polyps cause?
asymptomatic
what area are they usually in?
rectosigmoid area
how large are hyperplastic polyps?
small (<5mm)
what do they look like histologically, and what particular feature is seen?
well-formed glands or crypts lined by goblet or absorptive cells - infolding of the crowded epithelial cells with a "saw toothed" or serrated profile
what malignant potential do hyperplastic polyps have?
virtually none
what are juvenile polyps?
uncommon hamartomatous polyps
what disease can they be associated with, and who do they occur in?
associated with familial juvenile polyposis (or sporadic) and occurring inchildren younger than age 5
what symptom do juvenile polyps cause?
painless rectal bleeding after dfecation
where are most juvenile polyps located?
80% are located in the rectum
how large are juvenile polyps, and what are they shaped like?
large (1-3 cm in diameter), rounded, smooth with a stalk
what are glands like, and what is seen in them (2)?
cystically dilated glands, with: 1) ulceration and; 2) inflammation
when do juvenile polyps have malignant potential?
none in sporadic cases, but high risk in juvenile polyposis syndrome
what are hamartomatous polyps?
localized outgrowth of normal glands and smooth muscle
what syndrome must we know that hamartomatous polyps occur in?
Peutz-Jeghers syndrome
what other syndromes (2) were they mentioned to occur in?
1) Cowden; 2) Cronkhite-Canada
what is another name for inflammatory polyps, and who do they primarily occur in?
pseudopolyps - primarily in patients with inflammatory bowel disease
what are lymphoid polyps?
mucosal bumps containing lymphoid tissue
NEOPLASTIC POLYPS
what was said about neoplastic polyps, and their growth patterns?
different growth patterns of the same neoplastic process
what features does the malignant risk with adenomas correllate with (3)?
1) polyp size; 2) histologic architecture; 3) severity of dysplasia
what is the most common type of neoplastic polyp?
tubular adenomas (adenomatous polyps)
what is the least common type of neoplastic polyp?
villous adenomas
what is the most ominous type of neoplastic polyp?
villous adenomas
what is the largest type of neoplastic polyp?
villous adenomas
at what age are tubular adenomas most common?
after 60 (40-50%)
in what area are tubular adenomas most common?
rectosigmoid area
what are they like morphologically?
usually pedunculated with slender stalk and raspberry like heads
what type of appearance do they have histologically?
pseudostratification ("picket fence" appearance)
what are nuclei like?
elongated with hyperchromasia and increased nuclear-cytoplasmic ratio
what are villous adenomas like in architecture (composition)?
more than 50% villous
what symptoms come from villous adenomas (3)?
1) rectal bleeding; 2) hypoproteinemia; 3) hypokalemia
what are villous adenomas shaped like?
sessile, usually no stalk, with finger-like or branching papillae
what does sessile mean?
attached by the base
what other type of neoplastic polyp is there, and what is its composition like?
tubulovillous - usually 25-50% villous component
what are they usually shaped like?
pedunculated
DYSPLASIA
what is architecture like in high grade dysplasia (what type of arrangement)?
severe architectural complexity (back-to-back arrangement) and marked cytologic atypia
what metastatic potential do high grade dysplasias (CIS) have?
none
what % of removed colorectal adenomas are high grade dysplasias?
12%
what is the treatment, and what is the prognosis after treatment?
cured by endoscopic polypectomy
what is a "malignant polyp"?
colorectal adenoma containing invasive carcinoma
where is the invasive carcinoma located (layer)?
in the submucosa
what % of removed colorectal adenomas are "malignant polyps" (contain invasive carcinoma)?
5%
what is the metastatic potential of malignant polyps?
low
what is the normal treatment?
polypectomy alone
what is the treatment when there are poor prognostic factors?
colectomy
what are three poor prognostic factors for malignant polyps?
1) carcinoma at the resected margin; 2) poorly differentiated carcinoma; 3) lymphovascular invasion
what types of serrated adenomas exist (2)?
1) traditional; 2) sessile
what pathway are these involved in?
serrated polyp neoplasia pathway for colorectal cancer
HEREDITARY SYNDROMES - FAMILIAL ADENOMATOUS POLYPOSIS SYNDROME (FAP)
how many adenomas are seen in the GIT, and where (2)?
innumerable adenomas (average 1,000, at least 100) in the colon and small intestine
where are they particularly prevalent in the small intestine (2)?
1) around the ampulla of Vater; 2) around the stomach
what is the ampulla of Vater?
union of common bile duct and pancreatic duct
how is FAP inherited?
autosomal dominant
what gene is mutated, and what chromosome is it on?
APC gene, on chromosome 5q21
what fraction of cases have spontaneous mutation?
one third
at what age do adenomas begin to develop?
second and third decades
what is the incidence of malignant transformation?
very high - 100% at 40 years
what is the treatment?
prophylactic proctocolectomy
how is early detection done?
DNA marker (APC gene)
what treatment begins at age 12?
flexible sigmoidoscopy
how do variants of FAP arise?
APC mutations in different codons
what are the three variants?
1) attenuated FAP; 2) Gardner syndrome; 3) Turcot syndrome
what is attenuated FAP?
fewer than 100 adenomas, and later age of onset (44 for adenomas, 56 for cancer)
where does attenuated FAP occur?
preferentially in the right (ascending) colon
what is Gardner syndrome (3 things in addition to FAP)?
FAP + 1) fibromatosis; 2) multiple osteomas; 3) epidermal cysts
what is Turcot syndrome?
FAP + tumors of the CNS
what mutation occurs in most patients (2/3) and what mutation occurs in the other 1/3?
APC mutation in 2/3, germ-line defect in DNA mismatch repair in one third
JUVENILE POLYPOSIS SYNDROME
how is juvenile polyposis syndrome inherited?
autosomal dominant
how many polyps occur?
50-100
what genes have been identified (2)?
1) DPC4/SMAD4; 2) BMPR1A
what is there a high risk for?
GI adenocarcinoma, primarily colorectal cancer
PEUTZ-JEGHERS SYNDROME
how is this disease inherited, and what gene is often mutated?
autosomal dominant - LKB1/STK11 mutation (in 60% of familial and 50% of sporadic cases)
what type of polyps are seen?
hamartomatous polyps (large and pedunculated)
what % of cases involve the small bowel, colon, and stomach?
100%, 30%, 25%
what other sign is seen in PJS?
melanocytic mucosal and cutaneous pigmentation
where is it seen (5)?
1) lips; 2) oral mucosa; 3) face; 4) genitalia; 5) palmar surfaces
what is the malignant potential of PJS?
none
what is there increased risk of developing?
carcinomas (breast, lung, ovary, uterus)
HEREDITARY NONPOLYPOSIS COLORECTAL CANCER SYNDROME (LYNCH SYNDROME)
how is this condition inherited (mode of transmission, type of genes)?
autosomal dominant condition caused by inherited defects in DNA mismatch repair genes (hMSH2, hMLH1, hMSH6, hPMS1, hPMS2)
what do these mutations lead to?
microsatellite instability
what are microsatellites?
repeated sequences of DNA
what % of colon cancers does this represent?
5% of all colon cancers - the most common form of hereditary colon cancer
what is the risk for colon cancer in those with the genetic defects?
80-90%
what is the age of onset, and most common location?
early age of onset, right colon - cancers can be synchronous
how many adenomas occur?
low numbers <10-20
what is there an increased risk for?
extraintestinal cancer (especially endometrial)
COLORECTAL CARCINOMA
how does colorectal cancer rank in prevalence among visceral cancers and cancer deaths in the USA?
third most common visceral cancer and cancer death (150,000 new cases and 60,000 deaths each year)
in what populations is there the highest incidence?
high socioeconomic populations
why is incidence rising in "low risk" areas (Japan, Korea, etc)?
acquisition of "Western" lifestyle (diet) - among immigrants and descendants, rates rapidy reach those of the adopted country
what is the dietary etiology of colorectal carcinoma?
"Western" type of diet - high fat, low fiber
what other dietary factors are particularly associated with colorectal carcinoma (2)?
1) high calorie intake; 2) meat (particularly animal fat)
what foods have an inverse association with colorectal carcinoma (2)?
1) fiber; 2) vegetables
what is the increased risk for first degree relatives?
2 to 4 fold increased risk
what hereditary syndromes were mentioned to be associated with colorectal cancer (2)?
1) HNPCC; 2) FAP (classic, attenuated, Gardner, and Turcot syndrome)
what other diseases were mentioned to be associated with colorectal carcinoma (2)?
1) colorectal adenomas; 2) ulcerative colitis
what are the two pathologically distinct pathways that lead to colorectal carcinoma?
1) APC/Beta-catenin pathway; 2) serrated polyp neoplasia pathway
what concept do both pathways involve?
the "multi-hit" concept - stepwise accumulation of multiple mutations
what is the first hit in the APC/beta-catenin pathway?
APC at 5q21 (inherited or acquired)
what does the second hit involve?
beta-catenin - methylatin abnormalities, inactivation of normal alleles
what are hits farther down the line?
1) proto-oncogene mutation (K-RAS); 2) homozygous loss of cancer suppressor genes (p53, LOH, SMAD); 3) overexpression of COX-2; 4) additional mutations and gross chromosomal alterations (telomerase, many genes)
what mutations does the serrated polyp neoplasia pathway involve (2)?
1) BRAF mutation; 2) high DNA (CpG island) methylation (CIMP-high)
what formation does the serrated polyp neoplasia pathway start with?
hamartomatous polyps
what is the peak age of colorectal carcinoma?
7th decade
what % of cases occur before age 50?
20%
what is the most common location, and what % of cases occur there?
rectosigmoid colon (55% of cases)
how does colorectal carcinoma often present?
inconstant occult bleeding or change in bowel habit
what side is the lesion if there is unexplained anemia (iron deficiency anemia)?
generally right sided (ascending colon)
what other presentations will right sided lesions have (3)?
1) weakness; 2) weight loss; 3) right lower quadrant pain
how can left-sided (descending, sigmoid) lesions present (3)?
1) gross blood in stools; 2) small caliber "pencil stools"; 3) obstructive symptoms
what types of lesions are seen grossly on the left side?
encircling lesion (napkin-ring constriction)
what types of lesions are seen grossly on the right side (2)?
1) bulky cauliflower-like polypoid mass; 2) large sessile lesion
what is the most prevalent type of cancer microscopically, and what % of cancers are of this type?
95% adenocarcinoma
what test is positive in 60-70% of cases?
CEA
what is it a highly reliable indicator of?
recurrent tumor
what other tests can be used (list)?
fecal occult blood test (FOBT), fecal immunochemical test (FIT), digital rectal examination, flexible sigmoidoscopy, colonoscopy, double contrast barium enema, CT colonography ("virtual colonoscopy")
what is the single most important prognostic indicator?
extent of tumor at time of diagnosis (staging)
what is the system most widely used?
TNM classification and staging system (Tis, T1=4, NX, N0-2, MX, M0-1)
where was colorectal carcinoma said to spread (3)?
1) regional lymph node; 2) liver; 3) lung
DIVERTICULAR DISEASE (DIVERTICULOSIS)
who is this one of the most common GI diseases of?
elderly
what is the most common site?
sigmoid colon
where in the world is diverticulosis most common?
developed countries
what type of diet is a risk factor?
low fiber diet
what are underlying problems of diverticulosis (2)?
1) increased intraluminal pressure; 2) focal weakness in colonic wall
what is the usual clinical picture of diverticulosis like?
usually asymptomatic (80%)
where may pain occur?
left lower quadrant
what other symptoms may occur (list)?
constipation, diarrhea, rectal bleeding, fever, nausea, vomiting
what is seen grossly, and how big is it?
small flask -like or spherical outpouching (0.5 to 1 cm in diameter)
what is seen in the surrounding areas?
pronounced muscular hypertrophy
what is present in 10-25% of cases?
diverticulitis
what are complications of diverticular disease (5)?
1) bleeding; 2) muscular hypertrophy with obstruction; 3) pericolic abscess; 4) perforation; 5) fistula