Colonic and Rectal Polyps and Neoplasms Flashcards
(39 cards)
Rectal bleeding is bright red blood passed around or with the stool. It is extremely common and becomes more so with age.
Give a differential diagnosis for a patient with rectal bleeding
- haemorrhoids
- colorectal polyps or cancer
- anal fissures
- anal fistula
- IBD - crohn’s and UC
- diverticulitis
- trauma
- coagulopathies
- angiodysplasia
- anorectal varices
- proctitis
- intussusception
Constipation refers to bowels which open infrequently, and the faeces are hard and often cause pain during defacation.
Give a differential diagnosis for constipation
- general: pregnancy, inadequate fibre/diet, dehydration
- metabolic/endocrine: DM, hypercalcaemia, hypothyroidism, porphyria
- functional: dyschezia, IBS
- drugs: opiates, aspirin, anticholinergics, ca-ch blockers, antidepressants
- adynamic bowel: spinal cord lesions, Parkinson’s, Hirschprung’s, senility, myxoedema
- GI: obstruction, colonic disease (carcinoma, diverticular), aganglionisis, anal fissure, prolapsed piles
- defecatory disorders: rectal prolapse/intussusceptions, rectocoele, pelvic floor dysfunction, megarectum
What are adenomatous polyps?
- colorectal adenomas dervied from epithelial cells lining in mucosa
- v common, incidence increases w age
- at 60 years they are found in approx 20% of population
- adenomas may be sporadic or familial
- familal adenomas occur in syndromes such as FAP
If a patient is found to have a polyp, does that mean they have cancer?
- from naked-eye appearance: mass projecting from mucosal surface
- term ‘polyp’ tells us nothing about its biological behaviour
- may be benign, premalignant or malignant
What is meant by the following terms to describe a polyp?
- pedunculated
- sessile
- tubular
- villous
- tubulovillous
- pedunculated - attached to the normal mucosa by a stalk
- sessile - atttached to normal mucosa by broad base
- tubular - composed of tubular structures when looked at down microscope
- villous - composed of finger-like projections when looked at down microscope
- tubulovillous - contains mixture of tubular + villous architectures
Polyps are predominantly asymptomatic. However what are some clinical features that might be mentioned by a patient with polyps?
- rectal bleeding
- mucus discharges
- tenesmus
- changes in bowel habits, particularly urgency
- signs of anaemia
- fatigue
- sessile villous adenomas present with profuse diarrhoea and hypokalaemia
Many polyps are picked up incidentally when imaging is performed for other reasons
Are colorectal adenomas cancerous?
- no - they are dysplastic by definition
- pre-malignant, so left untreated may progress to adenocarcinoma
- in the GI tract, dyplasia is graded as low or high
Majority of adenomas will not progress to adenocarcinoma during a person’s lifetime. What are features associatd with a greater risk of progression?
- high grade dysplasia (rather than low grade)
- increasing size
- histological type (villous is higher risk than tubular)
Why is the term ‘adenoma’ in the GI tract confusing?
- in most contexts, an adenoma is a benign tumour of glandular epithelium which does not have the potential to become cancer (ie. adenomas are not premalignant)
- however in GI tract, term ‘adenoma’ is used for premalignant lesions
- by definition adenomas in GI tract are dysplastic (premalignant)
About 70% of colorectal cancers arise as a result of a (3) stepwise progression. What is this progression?
normal mucosa -> adenoma -> invasive adenocarcinoma
What is the progession to invasive adenocarcinoma due to?
accumulation of mutations in a number of critical growth-regulating genes:
- inappropriate activation of proto-oncogenes (eg. K-ras, c-myc)
- inactivation of tumour suppressor genes (eg. APC, TP53) - remember that both copies of tumour suppressor genes must be inactivated (‘two-hit’ hypothesis) since if only one allele for the gene is damaged, the second can still produce the correct protein
the exact order in which these mutations are acquired may very; it is the accumulation of mutations rather than their occurrence in a specific order which is most critical
Hence, use examples of genes to describe the process occurring from normal colon to carcinoma
What are the two pathways for developing colorectal cancers?
- 70%: chromosomal instability pathway (=adenoma-carcinoma pathway)
- 30%: microsatellite instability (MSI) pathway (= serrated pathway)
The large majority of pts who develop colorectal cancer through the adenoma-carcinoma pathway do so by acquiring sporadic mutations during life. These pts do not have a familial syndrome.
A small minority of pts who develop colorectal cancer through the adenoma-carcinoma pathway have a germline mutation in what gene?
- APC gene
- these pts have familial adenomatous polyposis
What is familial adenomatous polyposis?
- have germline mutation in one allele of APC gene
- other allele is normal
- FAP is a familial syndrome, inherited (autosomal dominant)
- although de novo germline mutations may account for up to 25% of cases
- affects 1 in 10,000
How/why do patients with FAP develop cancer?
- by following adenoma-carcinoma pathway sequence
- however, bc they have a germline mutation in the APC gene, every single cell in the body has the mutation (ie. every cell is already one step further along the pathway than in non-FAP patients)
- they develop hundreds of adenomatous polyps throughout the large intestine during their teens + 20s - t_he risk of development of an adenocarcinoma in one of these polyps is almost 100%_ by the age of about 40
- prophylactic panproctocolectomy is usually advised in these pts
FAP is thought to account for less than 1% of colorectal cancers (it is less common than Lynch syndrome). What is the mean age of developing colorectal cancer in FAP patients?
- 39 - compared to 70 in sporadic cases
FAP confers an increased risk of developing small intestinal adenomas/carcinomas - where, in particular?
- ampulla of Vater
What extra-intestinal manifestations is FAP associated with?
- desmoid tumours (locally aggressive tumor that does not metastasize)
- thyroid carcinomas
- osteomas (non-cancerous bony growths)
- congenital hypertrophy of the retinal pigmented epithelium
Fairly recently it has been recognised that ~30% cancers arise from an alternative pathway. What is this pathway?
- Microsatellite instability pathway (=serrated pathway)
- cancers arise from serrated polyps (also termed serrated “lesions”)
- called serrated as they have a serrated appearance microscopically
These serrated polyps may acquire sporadic mutations in a number of key genes, such as?
- activation of BRAF (an oncogene)
- silencing of mismatch repair genes (eg. MLH1, MSH2) due to hypermethylation of promotors. This results in microsatellite instability (MSI) - insertion or deletion of nucleotides within repeated sequences of DNA.
the accumulation of these mutations may lead to development of carcinoma
What is Lynch syndrome?
- familial syndrome, inherited (autosomal dominant)
- up to 5% of cases may be due to de novo mutations
- have germline mutation in one allele of a DNA mismatch repair gene
- other allele is normal
- a ‘second hit’ (eg. promotor methylation, second mutation) is present in the genome of tumours in patients with LS
Lynch syndrome: The order of frequency for germline mutation in the DNA mismatch repair gene is: MSH6 (most common), MSH2, MLH1, PMS2. What are the mismatch repair genes responsible for?
- recognising + repairing mistakes in DNA transcription
- which occur particualrly in areas of repeat DNA sequences (microsatellites) where DNA polymerases have a tendency to ‘slip’, either inserting extra or removing repeats.
- in the case of mononucleotide and dinucleotide repeat sequences this often leads to a frameshift mutation, resulting in a shortened non-functional protein
What cancers are patients with Lynch syndrome at risk of developing?
- Colorectal
- Endometrial - in women with LS, this is more common than colorectal cancer + it is more often the first (sentinel) cancer they develop
- Stomach
- Pancreatic
- Small bowel
- Ureter
- Renal pelvic
- Ovarian
