L21: Tumours of the Large Bowel Flashcards
Are tumours more common in the large bowel or the small bowel?
large bowel
What is a pedunculated polyp?
a polyp with a stalk
What is a sessile polyp?
flat polyp
What is a non-neoplastic polyp of the GIT?
- polyps that do not progress to a carcinoma
- do not become malignant
List the 4 main categories of non-neoplastic polyps
- hyperplastic
- hamartomatous
- inflammatory
- lymphoid
Where are hyperplastic normally found in the GIT?
recto-sigmoid colon
What are hyperplastic polyps? Why do they occur?
- non neoplastic polyps
- typically found in recto-sigmoid colon
- composed of non-neoplastic glands w/ goblet cell differentiation
- no malignant potential
result from delayed shedding of epithelial cells
Why do hyperplastic polyps occur?
result from delayed shedding of epithelial cells
What is a hamartoma?
an abnormal mixture of normal tissues and cells from the area in which it grows
What are juvenile polyps?
- non neoplastic polyps (no malignant potential)
- hamartomatous malformations of bowel mucosa
- children < 5 years usually
- occur in rectum typically
If an adult has juvenile polyps, what are these polyps called?
Retention Polyps
What are Peutz-Jegher polyps of the GIT?
- hamartomatous polyps
- small intestine + colon
- a/w Peutz-Jeghers Syndrome
Where in the GIT do Peutz-Jegher polyps occur usually?
small intestine + colon
What is Peutz-Jeghers Syndrome?
- hamartomatous syndrome
- AD
- a) mucocutaneous pigmentation
- b) have multiple hamartomatous polyps through GIT
Someone that has Peutz-Jeghers Syndrome is at an increased risk of developing what?
non-GI cancers (pancreas, breast, lung, ovary and uterus)
the polyps do NOT have malignant potential
List 3 hamartomatous syndromes of the GIT
- Peutz-Jeghers Syndrome
- Cowden Syndrome
- Cronkhite-Canada Syndrome
What is Cowden Syndrome?
- hamartomatous syndrome
- AD
- a/w PTEN mutation
- multiple hamartomatous polyps + trichoepitheliomas
Someone that has Cowden Syndrome is at an increased risk of developing what?
- thyroid or breast cancer
the polyps do NOT have malignant potential
What are the 3 characteristics of Cronkhite-Canada syndrome?
hamartomatous syndrome
- hamartomatous polyps
- nail atrophy
- skin pigmentation
Inflammatory (Pseudo)polyps are a type of non-neoplastic polyp. What disease are they associated with?
Inflammatory Bowel Disease - especially Ulcerative Colitis
What is another name for adenomatous polyps?
neoplastic polyps
What are the 3 types of adenomatous/neoplastic polyps?
- Tubular
- Villous
- Tubulovillous
Is a tubular adenomatous polyp more likely to be pedunculated or sessile?
pedunculated
Is a villous adenomatous polyp more likely to be pedunculated or sessile?
sessile
What is the treatment for adenomatous polyps?
Complete Excision:
- should be removed as they are considered pre-malignant
What is Familial Adenomatous Polyposis (FAP)?
- hereditary colon cancer syndrome
- AD
- mutation on APC gene on 5q21
- numerous polyps that can become cancerous
What is the mutation associated with Familial Adenomatous Polyposis (FAP)?
APC gene on 5q21
What is the treatment for Familial Adenomatous Polyposis (FAP)?
prophylactic total colectomy - entire colon needs to be removed
What is Gardner’s Syndrome?
- variation of FAP
- mutations of APC gene
- AD
- multiple adenomas, epidermoid cyst, fibromatosis, osteomas, abnormal dentition
Someone that has Gardner’s Syndrme is at an increased risk of developing what?
duodenal or thyroid cancer
What is Turcot’s Syndrome?
- variation of FAP
- mutations of APC gene
- AD
- colorectal adenomatous polyps and brain tumours
What syndrome is associated with colorectal adenomatous polyps and brain tumours?
Turcot’s Syndrome
List 2 syndromes that are variations of FAP
- Gardner’s Syndrome
2. Turcot’s Syndrome
In the adenoma-carcinoma sequence what is typically the first mutation present?
APC mutation
The Faecal Immunochemical Test (FIT) is used to screen for colon cancer by looking for…
testing faeces for occult blood
List some of the risk factors for colon adenocarcinoma
- increasing age
- adenomatous polyps
- hereditary syndromes
- IBD (especially ulcerative colitis)
- diet
- obesity
- physical inactivity
What is another term for Hereditary Non-Polyposis Colorectal Cancer (HNPCC)?
Lynch Syndrome
Why does Lynch Syndrome occur?
- due to microsatellite instability
- mutations in mismatch DNA repair genes
What mutations are present in Lynch Syndrome? [4]
mutations in mismatch DNA repair genes
- hMSH2
- hMLH1
- hPMS1
- hMPS2
What is Lynch Syndrome?
- AD familial
- colonic cancer - typically right sided
- there are 2 types
What is Lynch Syndrome 1?
a/w increased risk of colon cancer
What is Lynch Syndrome 2?
a/w increased risk of colon cancer and non-GI cancers (endometrial, ovarian)
Where does colon cancer arising from Lynch Syndrome normally occur?
right sided
How does right-sided colorectal carcinoma typically present?
- polypoid “cauliflower” lesions
- may ulcerate –> occult bleeding
- iron deficiency anaemia
How does left-sided colorectal carcinoma typically present?
- annular, encircling lesions
- constriction
- symptoms of obstruction
- rectal bleeding + changing bowel habits
Give 2 reasons why tumours of the left side present with obstruction
- lumen is narrower on left side
2. solid faecal material present
What are some of the symptoms of colorectal cancer?
- change in bowel habits
- blood in stool
- iron deficiency anaemia
Colonic carcinoma is a/w increased risk of endocarditis by what organism?
Streptococcus bovis
Where does colorectal carcinoma typically metastasize to first?
liver, lungs (think of blood circulation)
Do right-sided or left-sided lesions have a poorer prognosis?
left-sided lesions
What is the most common staging system used for colorectal adenocarcinomas?
Dukes’ Staging
What are the different stages of Dukes’ Staging of colorectal adenocarcinomas?
Dukes’ A = confined to the wall
Dukes’ B = invades through muscularis propria
Dukes’ C = nodal involvement
Dukes’ D = distant mets
What chemopreventive drug may be given to treat colon cancer?
COX Inhibitors (NSAIDs, aspirin…)
Why are COX inhibitors given when treating colorectal cancer?
because COX-2 has tumourigenesis effects (helps tumour propagation)
What is the MOA of Erbitux and Vectibix in treating colorectal cancer? (i.e. Cetuximab and Panitumumab respectively)
block the EGFR signalling pathway
What is the MOA of Avastin in treating colorectal cancer?
blocks the growth of blood vessels
How do carcinoid tumours of the GIT present?
- solitary, firm, yellow nodules
- form islands, glands or sheets
- monotonous
- speckled nuclei
- abundant pink cytoplasm
What 2 immunohistochemical stains can be used for carcinoid tumours?
- Synaptophysin
2. Chromogranin
What is Zollinger-Ellison Syndrome?
tumors cause the stomach to produce too much acid, resulting in peptic ulcers
– e.g. carcinoid tumour produces too much gastrin
What is Carcinoid Syndrome?
overproduction of serotonin by a carcinoid tumour
What is the clinical presentation of Carcinoid Syndrome?
- skin flushing
- diarrhea/cramps
- wheezing, cough
- hepatomegaly (from mets to liver usually)
What are Gastrointestinal Stromal Tumours (GISTs)?
- mesenchymal neoplasms of GIT
- arise from the pacemaker cells of GIT (Interstitial Cells of Cajal)
Which cells do GISTs arise from?
Interstitial Cells of Cajal - pacemaker cells of the GIT
What 2 mutations are associated with GISTs?
C-Kit (CD117)
PDGFRA
What medication/drug can be used for GISTs?
Gleevec (Imatinib) - tyrosine kinase inhibitors
List some risk factors for gastrointestinal lymphoma [4]
- H. pylori infection
- Coeliac disease
- Immunodeficiency
- Mediterranean lymphoma
List 3 monoclonal antibodies that can be used to treat metastatic colon cancer
- Cetuximab
- Panitumumab
- Bevacizumab
