L15 - Clinical Cases Flashcards
What are the T subcategories for TNM staging of colorectal cancer?
- TX: Primary tumour cannot be assessed
- T0: No evidence of primary tumour
- T1: Tumour invades submucosa
- T2: Tumour invades muscularis propria
- T3: Tumour invades subserosa or non-peritonealised tissues
- T4: Tumour perforates visceral peritoneum and / or directly invades other organs
- If the tumour is present in the mucosa but does not invade the submucosa, it is a dysplasia (not a cancer)
What are the N subcategories for TNM staging of colorectal cancer?
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastatic disease
- N1: Metastatic disease in 1-3 regional lymph nodes
- N2: Metastatic disease in 4 or more lymph nodes
What are the M subcategories for TNM staging of colorectal cancer?
- MX: Metastasis cannot be measured
- M0: Cancer has not spread to other parts of the body
- M1: Cancer has spread to other parts of the body
List the subtypes of colorectal adenocarcinomas.
Which subtype represents the majority of colorectal adenocarcinomas?
Colorectal adenocarcinomas are either:
1 - Microsatellite stable
2 - Microsatellite instable
- The majority (80%) are microsatellite stable
Why might the presence microsatellite instabilities imply that there is further genetic damage?
- Microsatellites are usually corrected by DNA mismatch repair
- If DNA mismatch repair is impaired, the microsatellites will remain
- Therefore, the presence of microsatellite instabilities implies that there is a defect in the cell’s DNA repair mechanisms
What are the characteristics of highly microsatellite instable (MSI-H) tumours?
MSI-H tumours are:
1 - Proximal, with a well-defined border
2 - Poorly differentiated
3 - Mucinous when examined histologically
4 - More likely to show lymphocytic infiltration
Give an example of a disease that predisposes patients to highly microsatellite instable (MSI-H) tumours.
Hereditary non-polyposis colorectal cancer (Lynch syndrome) predisposes patients to highly microsatellite instable (MSI-H) tumours
What inheritance pattern does Lynch syndrome show and which genes are affected?
- Autosomal dominant
- Mismatch repair (MMR) genes are affected in Lynch syndrome. Examples include:
1 - MSH2
2 - MSH6
3 - MLH1
In what proportion of colorectal tumours are RAS mutations present?
Why is this important clinically?
- RAS mutations are present in ~1/2 of all colorectal tumours
- Patients with tumours that have mutations in RAS are unlikely to benefit from anti-epidermal growth factor receptor (anti-EGFR) antibodies (because the MAPK pathway is dysfunctional)
In what proportion of colorectal cancers are BRAF mutations present?
Why is this important clinically?
- BRAF mutations are present in 8% of all colorectal tumours
- Patients with tumours that have mutations in BRAF usually have a poor prognosis (but it isn’t a negative marker for anti-EGFR therapy)
What is the primary difference between the distribution of affected lower GI tissue in Crohn’s disease and ulcerative colitis?
- In Crohn’s disease, it is usually the ileocaecal junction that is affected, but it can also occur in patches across the whole lower GI tract
- In ulcerative colitis, it is usually the distal colon and rectum that are affected
What mutation is present in von Hippel Lindau (VHL) syndrome and what is the impact of this?
- Germline mutation of VHL tumour suppressor gene (chromosome 3p) & second somatic mutation
- Mutations can cause accumulation of HIF⍺
