Chapter 17 Part 8 Flashcards
Where in the GI tract are polyps most common?
colon
rectum
What is the difference between sessile polyps and pedunculated polyps?
- sessile = small elevations of the mucosa
- pedunculated = with a stalk
What are the three types of benign polyps?
- hyperplastic
- inflammatory
- hamartomatous
What is the most common type of neoplastic polyp?
adenoma
Where and in what age group are hyperplastic polyps most commonly found?
- -descending colon
- -6th-7th decade of life
What is the theory behind how hyperplastic polyps are formed?
-result from decreased epithelial cell turnover and delayed shedding of surface epithelial cells, so goblet cells and absorptive cells “pile up”
What can the presence of a hyperplastic polyp be a clue for?
- an adjacent, more clinically important lesion
- -since epithelial hyperplasia can occur as a nonspecific rxn adjacent to (or overlying) a mass or inflammatory lesion
What is the morphology of hyperplastic polyps?
- less than 5 mm
- smooth, nodular
- on the crests of mucosal folds
- multiple
Clinically, it is important to distinguish hyperplastic polyps from what else?
- sessile serrated adenomas
- -histologically similar, but sessile serrated adenomas have malignant potential
Inflammatory polyps can be a part of which syndrome and what is its clinical triad?
- Solitary Rectal Ulcer Syndrome (SRUS)
- rectal bleeding, mucus discharge, lesion on anterior rectal wall
What is the cause of inflammatory polyps in SRUS?
-impaired relaxation of anorectal sphincter that creates a sharp ledge at the anterior rectal shelf and leads to recurrent cycles of injury and healing
What is the distinctive histological feature of inflammatory polyps?
–mixed inflammatory infiltrates, erosion, and epithelial hyperplasia … all together with prolapse-induced fibromuscular hyperplasia of the lamina propria
True or False: many hamartomatous polyp syndromes are caused by germline mutations in tumore suppressor genes or proto-oncogenes
True, so some of these syndromes are associated with increased cancer risk
What are two syndromes associated with hamartomatous polyps?
- -Juvenile Polyposis
- -Peutz-Jeghers Syndrome
The vast majority of juvenile polyps occur in what age group?
younger than 5 yrs
-the infantile form is severe
What is the typical location and presentation of juvenile polyps?
- rectum
- rectal bleeding
-maybe intussusception, intestinal obstruction, or polyp prolapse through the anal sphincter
True or False: sporadic juvenile polyps are often solitary
True; referred to as “retention polyps”
What is the inheritance pattern of the genetic form of juvenile polyposis?
autosomal dominant
–3-100 hamartomatous polyps that may require colectomy to limit the chronic (and sometimes severe) hemorrhaging associated w/ polyp ulceration
What are extraintestinal manifestations of juvenile polyposis?
- congenital malformations
- digital clubbing
- pulmonary arteriovenous malformations
True or False: dysplasia is common in syndromic juvenile polyposis
True; early colon cancer (45% by age 45)
What is the morphology of juvenile polyps?
- less than 3 cm
- pedunculated
- smooth, red surface
- cystic spaces characteristic after sectioning
- dilated glands filled w/ mucin and inflammatory debris
What is the most common gene mutated in juvenile polyposis?
SMAD4
What is the inheritance pattern of Peutz-Jeghers Syndrome and the median age of onset?
- autosomal dominant, but it’s rare
- 11 yrs old
What is the GI presentation of Peutz-Jeghers Syndrome and the cutaneous presentation?
- multiple GI hamartomatous polyps
- hyperpigmentation of lips, nostrils, buccal mucosa, palms, genitalia, and perianal region (dark blue to brown macules)
What are two important severe complications of Peutz-Jeghers Syndrome?
- polyps can initiate intussusception, often fatal
- marked increase for malignancies: sex cord tumors of the testes, gastric and small intestine cancers, colon, pancreatic, breast, lung, ovarian, and uterine cancers
What is the genetic mutation in Peutz-Jeghers Syndrome?
loss of fxn mutation in STK11 ( tumor suppressor gene that encodes serine/threonine kinase 11, which regulates cell polarization)
Where in the GI tract are polyps of Peutz-Jeghers most common?
small intestine
What is the gross appearance of Peutz-Jeghers polyps?
- large
- pedunculated
- lobulated
What is the histologic appearance of Peutz-Jeghers polyps that differentiates them from juvenile polyps?
-arborizing network of connective tissue, smooth muscle, lamina propria, and glands … lined by normal intestinal epithelium
What is the most common patient population for adenomatous polyps?
- slight male predominance
- present in 30% of people by age 60 yrs
Adenomatous polyps are a precursor to what type of cancer?
colorectal adenocarcinoma
At what age should people start getting screened for colon cancer?
45-50
–unless you’re in a high-risk group, then screenings should begin 10 yrs prior to the youngest age at which a relative was diagnosed
True or False: colorectal adenomas are characterized by the presence of epithelial dysplasia
True
-hallmarks of epithelial dysplasia are: nuclear hyperchromasia, elongation, and stratification
True or False: regular surveillance colonoscopy and polyp removal reduce the incidence of colorectal adenocarcinoma
True
What is the most important characteristic of an adenoma that correlates it with the risk of malignancy?
- size
- 40% of polyps larger than 4 cm had a foci of cancer, but it’s only specific to that polyp, not others
What is the inheritance pattern of Familial Adenomatous Polyposis?
autosomal dominant (75% are inherited, 25% are de novo mutations)
-somatic mutation in APC gene, which is a negative regulator in the Wnt pathway (chromosomal instability)
What extraintestinal manifestation of FAP can be detected at birth?
-hypertrophy of the retinal pigment epithelium
What is the minimum required number of polyps to be diagnosed as FAP?
100, but thousands may be present by teen years
-morphologically indistinguishable from sporadic adenomas
What is the cancer risk in FAP?
-100% of patients develop colorectal adenocarcinoma (often before age 30), but almost always by age 50
What are common extracolonic sites of adenomas in FAP patients?
- hepatopancreatic ampulla
- stomach
What is the prophylactic treatment for individuals with the APC mutation?
standard therapy is a colectomy
What is the most common malignancy of the GI tract?
colonic adenocarcinoma
What is the pathogenesis pathway for FAP-induced colonic adenocarcinoma?
- -adenoma-carcinoma sequence
- -chromosomal instability
- -(APC/Wnt)
- -KRAS, SMAD2, SMAD4
- -p53
What is the peak age and dietary risk factors for colonic adenocarcinoma?
- -60-70 yrs
- -low fiber, high fat, high refined carbs
What drug can be used for pharmacologic chemoprevention of colonic adenocarcinoma?
ASA/NSAID’s because they inhibit COX2 which is necessary to produce prostaglandin E2
(prostaglandin E2 promotes epithelial proliferation)
What is the pathogenesis pathway for HNPCC (Lynch Syndrome)?
- Microsatellite Instability Pathway
- DNA mismatch repair
Where in the colon is cancer in patients with HNPCC (Lynch Syndrome)
-ascending colon
Where in the body are additional cancer risks for individuals with Lynch syndrome?
- endometrium
- ovaries
- stomach
- brain/CNS
- urinary tract
What is the most common syndromic form of colon cancer?
HNPCC
The majority of patients with HNPCC (Lynch Syndrome) have mutations in which genes?
MLH1
MSH2
The chromosomal instability pathway (APC) is associated with what form of adenoma?
- tubular
- villous
The microsatellite instability pathway (MLH1, MSH2) is associated with what form of adenoma?
-sessile serrated
True or False: colonic carcinomas in the distal colon tend to be annular
True; “napkin ring” constrictions that narrow the lumen
-proximal colonic carcinomas extend along one wall and rarely cause obstruction
How are right-sided colon cancers most often called to attention?
-fatigue and weakness due to IDA
“IDA in an older man or a post-menopausal woman is GI cancer until proven otherwise”
What is the clinical presentation of left-sided colon cancers?
- occult bleeding
- change in bowel habits
- cramping
- LLQ discomfort
What are the two most important factors for prognosis of colonic adenocarcinoma?
- depth of invasion
- lymph node metastasis
-also poor differentiation and mucinous histology
`What is the most common site of metastatic lesions of colonic adenocarcinoma?
-liver (due to portal drainage)
