Week 7 GI Neoplasia

Question 1

What test is the best to look for hidden blood in stool?

Answer 1

The Quantitative Faecal ImmunochemicalTest(qFIT)

Question 2

How does a qFIT differ from the guaiac based FOBtest?

Answer 2

qFIT look for the globin part of human haemoglobin so is highly specific.

Guaiac-based fecal occult blood test (gFOBT) looks for the haem portion of haemoglobin and can test postivie if there is red meat in the diet or other things like certain meds or vegitables so is less specific.

Question 3

A biopsy of a polyp is taken after a colonoscopy.

Area A – Dysplastic glands forming tubular and villous structures - What is this part defined as?
Area B - Abnormal glands invading the wall of the colon with a stromal reaction – What is this part defined as?

Answer 3

A: Adenoma

B: Adenocarcinoma

Question 4

What are the 3 histological features of an adenocarcinoma in the colon?

Answer 4

1. High nucleus/cytoplasm ratio - implies cell is new growth - common in cancer cells
2. Hyperchromasia - cell nucleus is darker stained - implies more dense DNA
3. Pleomorphism - cells are varying in size and shape - implies they are abnormal

Question 5

On a histological sample what would these three things imply?

1. High nucleus/cytoplasm ratio
2. Hyperchromasia
3. Pleomorphism

Answer 5

Malignancy

Question 6

What would you interpret from this histology report from a colon polyp biopsy?

• Area A – Dysplastic glands forming tubular and villous structures – adenoma
• Area B - Abnormal glands invading the wall of the colon with a stromal reaction – adenocarcinoma

The tumour cells show the cytological features of malignancy:
* High nucleus/cytoplasm ratio
* Hyperchromasia
* Pleomorphism

Answer 6

The polyp is an adenoma however the adenoma has progressed to form an adenocarcinoma, which is invading the base of the polyp.

Question 7

Three types of colonic polyps:

• Hyperplastic ( metaplastic)
• Adenoma
• A special type of hyperplastic polyp called serrated polyp

Rank form most to least chance of developing malignancy

Answer 7

• Adenoma - high potential
• A special type of hyperplastic polyp called serrated polyp - some potential
• Hyperplastic ( metaplastic) - no potential

Question 8

What is the general stepwise progress of gene alteration that leads form adenoma to adenocarcinoma?

Answer 8

Mutational activation of oncogenes and inactivation of tumour suppressor genes

Question 9

Is the APC genean oncogene or a tumour suppressor?

Answer 9

Tumour suppressor

Question 10

Is p53 and oncogene or a tumour suppressor?

Answer 10

Tumour suppressor

Question 11

What does persistent diarrhoea (lack of day-day variability) hint to?

Answer 11

R side colon cancers ( ascending colon and caecal tumours)

Question 12

Another word for the muscularis externa?

Answer 12

Muscularis propria

Question 13

Describe the TNM staging mechanism for GI cancer?

Answer 13

• Tis means the cancer is at its earliest stage (in situ). It is growing into the mucosa but no further.
• T1 in the submucosa
• T2 in the muscularis externa
• T3 into the outer layer of the bowel wall (serosa).
• T4 means the tumour has grown through the outer layer of the bowel wall (serosa)

A tumour at this stage can be described as T4a or T4b:

• T4a means the tumour has caused a hole in the bowel wall (perforation) and cancer cells have spread outside the bowel.
• T4b means it has grown into other nearby structures, such as other parts of the bowel or nearby organs.

N is the number of nodes it has grown into

• N0 means no lymph nodes contain cancer cells.
• N1 means there are cancer cells in up to 3 nearby lymph nodes
• N2 means there are cancer cells in at least four or more nearby lymph nodes

M – Metastases

• M0 means the cancer has not spread to distant organs.
• M1 means the cancer has spread to distant organs such as the liver or lungs or it has spread to distant parts of the tissue that covers the outside of the bowel and other organs (peritoneum).

Question 14

What is the most common site of metastasis from colon cancer?

Answer 14

Liver

Question 15

What are the 4 top sites for colorectal cancer?

Answer 15

1. Rectum
2. Sigmoid
3. Caecum
4. Ascending colon

Question 16

Is rectum/sigmoid cancer more common in men or women?

Answer 16

Men

Question 17

Is caecum/ascending colon cancer more common in women or men?

Answer 17

Women

Question 18

Main difference in presentation between caecum/ascending colon cancer and rectum/sidmoid cancer?

Answer 18

Rectum/sigmoid: More likely to see blood in rectum/sigmoid

Caecum/ascending: Diarrhoea constant

Question 19

What is routine for anyone over the age of 50?

Answer 19

Population over the age of 50 routinely and regularly checked for occult blood (qFIT)

Question 20

What does removing an adenoma do?

Answer 20

Curative -> can’t progress to adencarcinoma

Question 21

What clinical effects can still arise form benign tumours?

Answer 21

• Bleeding – erosion and ulceration
• Space occupying lesions within skull
• Compression of adjacent structures
• Obstruction of lumina
  – e.g. intussusception in GI tract
• Hormonal effects
  – increased production
  – decreased production

Question 22

How can a bowel polyp lead ot ischaemia?

Answer 22

The polyp gets dragged during peristalis causing telescoping of the bowel.

This then compresses the mesentary leading to ischaemia

Question 23

What are the two main categories of borderline tumours?

Answer 23

1. Tumours that show extensive local invasion but almost never
   metastasise. These are prone to local recurrence if
   incompletely excised.
2. Tumours that appear entirely benign at the time of diagnosis,
   but which can develop distant metastases, often presenting
   many years after the initial diagnosis.

Question 24

Most ocmmon type of oesophageal carcinoma worldwide

Answer 24

Squamous cell carcinoma

Question 25

Most ocmmon type of oesophageal carcinoma in uk

Answer 25

Adenocarcinoma

Question 26

Where does a squamous cell carcinoma and adenocarcinoma in the oesophagus occur? What are the common causes of both

Answer 26

Upper oesophagus -> squamous cell carcinoma -> smoking Lower -> adenocarcinoma -> acid reflux/ GORD

Question 27

What is the actual definition of barrett's oesophagus?

Answer 27

Metaplasia from squamous epithelium to columnar epithelium

Question 28

What is the most important factor for oesophageal carcinoma prognosis?

Answer 28

Tumour STAGE is the most important prognostic factor for both squamous cell carcinomas and adenocarcinomas – Good prognosis for tumours confined to the mucosa – 10-20% survival for adenocarcinomas involving deep muscularis propria

Question 29

What is the TNM staging for oesophageal cancer? Don't have to remember details of structures

Answer 29

Question 30

What is the geographical incidence of gastric adenocarcinoma?

Answer 30

Highest rates in Japan and east Asia, eastern Europe and parts of S America

Question 31

What is the TNM staging for gastric cancer? Don't have to remember details of structures

Answer 31

Question 32

Main non geographical demographic aspects to gastric cancer?

Answer 32

* Incidence increases with age * Males > females * Often presents late

Question 33

Two main histological patterns observed in gastic cancer

Answer 33

– Intestinal * Histological gland formation * The majority of cases in high incidence areas * Increased risk in patients with Familial Adenomatous Polyposis (FAP) – Diffuse * Histologically sheets of “signet ring” cells * Relatively more common in low incidence areas * Often younger patients * Female > male * Mutation or inactivation of CDH1 gene a common feature * May show linitis plastica (“leather bottle stomach”) appearance rather than a polypoid tumour macroscopically

Question 34

What is Familial Adenomatous Polyposis (FAP)

Answer 34

Familial Adenomatous Polyposis, a hereditary cancer syndrome caused by mutations in the APC gene. Leads to hella polyps

Question 35

What is a Neuroendocrine tumour? (NETs)

Answer 35

Epithelial tumours associated with the synthesis of hormone or neurotransmitter-like substances

Question 36

Types of neoplasia in the small bowel

Answer 36

* Adenocarcinoma * Neuroendocrine tumours * GISTs * Lymphoma

Question 37

What is a Gastrointestinal stromal tumour (GISTs)

Answer 37

* Soft tissue tumour that can arise anywhere in the GI tract – Related to “pacemaker” cells in the muscularis propria – Malignant tumours are a type of sarcoma – 75-80% of GISTs have activating mutations in the KIT receptor tyrosine kinase gene Hint: Kit is sarcastic get the gist?

Question 38

Histology patterns of Gastrointestinal stromal tumour (GISTs)

Answer 38

“Epithelioid” pattern “Spindle cell” pattern

Question 39

Types of colorectal polyps

Answer 39

* Inflammatory – IBD, lymphoid * Hamartomatous * Hyperplastic * Lesions in the submucosa e.g. lipoma presenting as a “polyp * Neoplastic - Adenomas

Question 40

What is a harmatoma

Answer 40

A hamartoma is a benign (non-cancerous) growth made up of an abnormal mixture of normal tissues and cells that are native to the organ or site where it occurs — just disorganized or excessive in quantity.

Question 41

What is true about deactication of APC gene and colorectal adenocarcinomas and FAP

Answer 41

Inactivation of APC (Adenomatous Polyposis Coli) tumour suppressor gene seen in about 80% of colorectal carcinomas. FAP is where you inherit a mutation in APC and if untreated almost always leads to cancer. However you can develop a mutation in APC without FAP. Only 1% of colorectal carcinomas are caused by FAP

Question 42

What is KRAS

Answer 42

Proto-oncogene

Question 43

WHat are TP53, SMAD2, SMAD4

Answer 43

Tmour supressor genes

Question 44

What are MSH2, MLH1

Answer 44

DNA mismatch repair genes Inactivation of these is a pathway to adenocarcinoma but not a typical one.

Question 45

What is Lynch syndrome

Answer 45

Inherited mutation in either of the DNA mismatch repait genes MSH2, MLH1 Hint: People back in day who tried to repair racial missmatch got lynched

Question 46

What is the “Serrated neoplasia” pathway to colorectal cancer?

Answer 46

Typically have a mutation in either BRAF or KRAS protooncogenes. More common in the right colon

Question 47

What familial condition more commonly leads to colo rectal carcinomas. FAP or Lynchs?

Answer 47

* About 1% of colorectal carcinomas are associated with FAP * Up to 5% associated with Lynch syndrome

Question 48

What is the TNM staging for colorectal cancer detailed (don't to know deets)

Answer 48

Question 49

What normally happens after a positive qFIT

Answer 49

Referral for colonoscopy

Question 50

What is a problem with qFIT? What is done to compensate for this?

Answer 50

High false positive rate Often done twice

Question 51

Colonoscopy risks

Answer 51

– Bleeding risk ~1 in 400 – Bleeding requiring admission ~1 in 2000 – Perforation risk ~1 in 2500