L1 – Colorectal Pathology Flashcards
What are the main pathways in colorectal cancer development?
Colorectal cancer develops via distinct pathways including chromosome instability (CIN), microsatellite instability (MSI), and the serrated neoplasia pathway.
How is colorectal cancer described in terms of heterogeneity?
It is a heterogeneous disease that evolves through stepwise genetic and epigenetic alterations.
What is the worldwide incidence trend of colorectal cancer?
Colorectal cancer shows significant geographical variation with sporadic and familial cases, and its incidence is influenced by lifestyle and dietary factors.
Why is recognising the genetic pathways in colorectal cancer important?
Understanding these pathways aids in diagnosis, prognosis, and may inform targeted therapeutic approaches.
Which risk factors predispose to colorectal carcinoma?
Age, obesity, physical inactivity, alcohol consumption, inflammatory bowel disease, schistosomiasis, and family history of colorectal neoplasia.
How do dietary factors influence colorectal cancer risk?
Diets low in fibre and high in refined carbohydrates and beef increase risk, partly due to longer transit times and bile acid conversion into carcinogens.
What role do polyposis syndromes play in colorectal cancer?
Syndromes such as familial adenomatous polyposis and Lynch syndrome cause early-onset colorectal neoplasia through inherited mutations (e.g. APC, MLH1).
How do genetic abnormalities contribute to the adenoma–carcinoma sequence?
Sequential mutations—starting with APC, then KRAS, TP53 and others—drive the progression from benign adenoma to malignant carcinoma.
What is the definition of a polyp in colorectal pathology?
A polyp is a protuberant growth arising from epithelial or mesenchymal tissues, which may be benign or malignant.
Name the major types of colorectal polyps.
Inflammatory, hamartomatous, neoplastic (e.g. adenomas, adenocarcinomas), and other types such as hyperplastic polyps.
How does a hamartomatous polyp differ from an adenomatous polyp?
Hamartomatous polyps are benign tumour-like lesions containing multiple differentiated tissues, whereas adenomas are neoplastic and can progress to carcinoma.
What is the clinical significance of adenomatous polyps?
Over 95% of colorectal adenocarcinomas arise from adenomatous polyps, making their detection and removal critical.
What genetic changes mark the CIN pathway?
The CIN pathway involves aneuploidy, somatic copy number alterations, and mutations in genes like APC, KRAS, and TP53.
How does the MSI pathway differ from the CIN pathway?
MSI tumours, often seen in Lynch syndrome, result from mutations in DNA mismatch repair genes and are characterised by frequent base pair mutations in microsatellites.
What genetic abnormality is typically associated with serrated polyps?
Activating mutations in the BRAF oncogene are commonly associated with serrated neoplasia.
Why is the order of genetic alterations important in the adenoma–carcinoma sequence?
The sequence of alterations influences the histological progression and potential for invasive cancer development.
How does chronic inflammation, such as in inflammatory bowel disease, promote colorectal carcinogenesis?
Persistent inflammation leads to DNA damage and a microenvironment that favours neoplastic transformation.
How do bile acids contribute to the risk of colorectal cancer?
Bile acids, when converted into secondary carcinogens, can damage the colonic mucosa and promote mutations.
What is the impact of fibre intake on colorectal cancer development?
High fibre diets reduce transit time and dilute potential carcinogens, lowering the risk of neoplastic changes.
How does loss of heterozygosity (LOH) affect tumour suppressor genes in colorectal cancer?
LOH results in the inactivation of key tumour suppressors, removing crucial controls over cell proliferation.
How can molecular testing assist in risk stratification of colorectal polyps?
It identifies mutations (e.g. KRAS, BRAF) that help predict the likelihood of progression to malignancy.
What is the clinical relevance of distinguishing sporadic from familial colorectal cancers?
Familial cases (e.g. Lynch syndrome, FAP) may require early screening and genetic counselling due to their distinct genetic basis.
How does the serrated neoplasia pathway differ morphologically from the traditional adenoma–carcinoma sequence?
Serrated lesions exhibit a saw-tooth epithelial pattern and often progress via BRAF mutations, sometimes more rapidly.
In what way does microsatellite instability (MSI) affect chemotherapy response in colorectal cancer?
MSI-high tumours can respond differently to certain chemotherapies and generally have a distinct prognosis compared with CIN tumours.
