pathology 6 - Colonic polyps Polyposis syndromes Lynch syndrome Colorectal cancer Molecular pathogenesis of colorectal cancer Flashcards
A man has a biopsy of a colonic polyp. The more ____ (villous/sessile/tubular/hyperplastic) it is, the more likely that it is malignant.
Villous
Your 50-year-old patient has a history of hyperplastic polyps. On colonoscopy, where do you most expect to find new hyperplastic polyps?
In the rectosigmoid area
A child with rectal discomfort has a single rectal juvenile polyp on colonoscopy. He is otherwise well. Should be polyp be urgently removed?
No; there is no malignant potential if it is truly the only juvenile polyp
The malignancy risk of adenomatous polyps is not associated with ____ (degree of dysplasia/villous histology/size/symptoms).
Symptoms
What type of polyp is considered a precursor for colorectal cancer?
Adenomatous polyps
List these three adenomatous polyp subtypes in order of their potential for malignant transformation, from lowest to highest.
Tubular adenomas, tubulovillous adenoma, villous adenomas
What two conditions are associated with the formation of hamartomatous polyps?
Peutz-Jeghers syndrome and juvenile polyposis
adenomatous colonic polyps genes
APC and KRAS, which are commonly mutated via the chromosomal instability pathway in neoplastic polyps
A patient has a colonoscopy. Polyps are biopsied, and “saw tooth” crypts are seen. Is there a risk of progression to colorectal cancer?
Yes, as the biopsy description is consistent with serrated polyps, which are premalignant (~20% of sporadic colorectal cancer cases)
What genetic mutations are associated with serrated polyps?
The CpG hypermethylation phenotype pathway with microsatellite instability, and mutations in BRAF
A 12-year-old boy is found to have several polyps in his colon, stomach, and small bowel. For what cancer is he at risk?
Adenocarcinoma (this is likely juvenile polyposis syndrome)
A man has GI tract hamartomas and dark patches around his mouth and palms. He asks if his son will be affected by this disorder. Your reply?
The probability is 50% (this patient has Peutz-Jeghers syndrome, an autosomal dominant disorder)
A patient has multiple GI tract hamartomas and hyperpigmented hands, mouth, lips, and genitalia. What cancers is he at increased risk for?
Increasing risk for colorectal, breast, stomach, small bowel, pancreatic cancers (the patient has Peutz-Jeghers syndrome)
A patient inherits a mutation of the APC gene on chromosome 5q. He asks about his risk for colorectal cancer. What do you tell him?
The patient has familial adenomatous polyposis syndrome; there is 100% progression to CRC if the colon is not removed
A 28-year-old man with a history of familial adenomatous worries about his newborn son and asks what the inheritance pattern is.
Autosomal dominant (patients inherit one faulty copy of the gene and lose the other through an acquired mutation [two-hit hypothesis])
Familial adenomatous polyposis involves mutation of the ____ gene on chromosome ____. This disease follows the ____ hypothesis
APC, 5q; two-hit
A patient with bone and soft tissue tumors is found to have thousands of polyps on colonoscopy. What syndrome is suspected?
Gardner syndrome
Why might you want to perform a colonoscopy on a young patient with extra teeth and abnormally pigmented retinas?
These are Gardner syndrome traits (FAP, osseous/soft tissue tumors, hypertrophy of retinal pigment epithelium, impacted/supernumerary teeth)
A young patient with a history of a brain tumor has GI bleeding. What syndrome might you want to urgently screen for in your work-up?
Turcot syndrome (FAP + malignant CNS tumor) (Turcot = Turban)
What is the inheritance pattern of juvenile polyposis syndrome? At what age does it typically present?
Autosomal dominant; less than 5 years of age
A woman is diagnosed with endometrial cancer and has multiple relatives with skin and colorectal cancer. What syndrome do you suspect?
Lynch syndrome, or HNPCC (requires 3 relatives with Lynch syndrome across 2 generations, at least 1 found before age 50)
Hereditary nonpolyposis colon cancer, or Lynch syndrome, involves mutations of DNA ____ genes. It is of autosomal ____ inheritance.
Mismatch repair; dominant
If working up a patient for HNPCC, what part of the bowel do you biopsy? What gene mutation would you look for in the biopsied tissue?
The proximal colon (is always involved); screen for mutations of DNA mismatch repair genes with subsequent microsatellite instability
What percentage of patients with HYPNCC will progress to have colorectal cancer?
Approximately 80%
A patient is diagnosed with right-sided colon cancer. What type of symptoms would you observe in this patient to reach your diagnosis?
An exophytic mass, iron deficiency anemia, weight loss
Name at least three risk factors for colorectal cancer
Adenomatous and serrated polyps, familial cancer syndromes, IBD, tobacco use, diet of processed meat with low fiber
How do you screen for colorectal cancer?
Colonoscopy, flexible sigmoidoscopy, or stool occult blood testing
A patient with past history of colorectal cancer is constantly monitored for recurrence. What nonspecific serum tumor marker is used?
Carcinoembryonic antigen (CEA)
A man has fevers, hypotension, and a new murmur. Blood cultures grow a streptococcal species. Why might you want to perform a colonoscopy?
lthough rare, colorectal cancer can be associated with Streptococcus bovis bacteremia (this patient may need a colonoscopy once stabilized)
A male patient with iron deficiency anemia is concerned about colon cancer risk. Should he be concerned? Who else should be concerned?
Yes, as iron deficiency anemia can be a presenting sign of colorectal cancer, from occult GI bleeding; postmenopausal females
Put in order (from most to least common) where colorectal cancer presents: descending colon, ascending colon, rectosigmoid junction.
Rectosigmoid junction, ascending colon, descending colon
A man is worried about colon cancer. He wants a screening CEA level drawn, because he is “scared of colonoscopies.” What do you tell him?
CEA levels cannot be used for screening—they can be used only to monitor for recurrence in previously diagnosed patients
In the microsatellite instability pathway, what type of mutation is responsible for carcinogenesis in colonic epithelium?
DNA mismatch repair gene mutations, which accumulate (they occur sporadically or are defective in Lynch syndrome)
The KRAS gene mutation leads to dysregulation of what cellular function?
Signal transduction (the cell will respond abnormally to growth factors, contributing to tumorigenesis)
Both ____ and ____ gene mutations must be present for colonic adenoma formation. The ____ gene mutation alone simply puts the colon at risk.
APC, KRAS; APC
Loss of function of which tumor suppressor genes is often the last step in malignant transformation of colonic epithelial cells?
p53, DCC
What molecular pathway most commonly generates sporadic colorectal cancer?
APC/β-catenin (chromosomal instability) pathway
A patient has a family history of Lynch syndrome due to genetic microsatellite instability. Are there any physical signs other than cancer?
There are none, despite the accumulation of mutations (no defined morphologic correlates)
APC gene mutations lead to dysregulation of what cellular function? Can any gross findings be seen on colonoscopy?
Intercellular adhesion (there is decreased intercellular adhesion and increased proliferation); no, as the colon will appear normal
In the CRC chromosomal instability pathway, indicate whether each gene in the sequence is a tumor suppressor or a proto-oncogene.
APC is a tumor suppressor, KRAS is a proto-oncogene, p53 and DCC are tumor suppressors
