Intestinal Neoplasia

Question 1

What type of cancer are most colorectal cancers?

Answer 1

Adenocarcinomas (carcinomas of glandular origin) arising from the glandular epithelium which lines the mucosa

Question 2

List some of the possible types of colorectal cancer.

Answer 2

Adenocarcinoma
Small cell carcinoma
Sqaumous cell carcinoma
Metastatic carcinoma (mucosal or serosal deposits)
Adenosquamous carcinoma
Undifferentiated carcinoma
Endocrine tumour
Mixed carcinoid-adenocarcinoma
Lymphoma

Question 3

What is dysplasia?

Answer 3

Development of non-malignant cellular abnormalities

- small amount of genetic change increases risk of becoming malignant

Question 4

What are colonic adenomas?

Answer 4

Dysplastic, benign, glandular neoplasms

Most as polyps

Question 5

What does cribiform mean, and how can it relate to colonic neoplasms?

Answer 5

Cribiform - something is pierced by lots of holes

Hyperplasia of cells into adenomas/adenocarcinomas can have bad architecture and cribiform areas

Question 6

What are the differential diagnoses of an adenoma?

Answer 6

Hyperplastic (metasplatic) polyps
Haemartomatous polyps
Inflammatory polyps
Submucosal lesions (e.g. lipoma or leiomyoma)

Question 7

What are the risk factors for developing colorectal carcinoma?

Answer 7

Adenoma - size (>2cm) and number
IBD - mainly ulcerative colitis
Family history
Other carcinomas
- cancer from epithelial cells 
Polyposis syndromes

Question 8

When should you be worried about malignancy with a benign polyp?

Answer 8

Polyp is >2cm
Flat polyp with villous pattern have a larger surface area and no stalk, and so are more likely to become malignant
Grade of dysplasia - the higher the grade the greater the risk of malignancy

Question 9

What is familial adenomatous polyposis?

Answer 9

Inherited disorder of the colon and rectum
- APC (autosomal dominant)
- MUTYH (recessive)
Marked increase in adenoma’s (polyps or flat)
Average age of progression to carcinoma is 39

Question 10

Describe the pathophysiology associated with APC gene mutation.

Answer 10

Via phosphorylation of beta-catenin, APC protein controls activation of transcription factors within cells
This in turn affects expression of a variety of genes that can change the proliferation and differentiation state of the cells

Question 11

What is Lynch Syndrome?

Answer 11

Hereditary non-polyposis colonic carcinoma (HNPCC)
- MLH1, MSH2, MSH6 and PMS2 genes affected
Endometrial carcinoma is also common
(and stomach, SI, liver, gallbladder ducts, upper urinary tract, brain, skin and prostate)

Question 12

How does Lynch syndrome lead to colonic carcinoma?

Answer 12

Loss of function of DNA mismatch repair genes results in a rapid development of genetic abnormalities
Adenocarcinoma sequence progresses at a faster rate in these patients

Question 13

Describe the T stage when staging colonic carcinoma’s.

Answer 13

T1 - invasion of the submucosa, but not into the muscularis propria
T2 - invasion into, but not all the way through, the muscularis propria
T3 - invasion through the muscularis propria, but not breaching the serosal surface or invading other organs
T4a - invasion of other organs
T4b - breach o the serosal surface

Question 14

Describe the N stages of colorectal cancer staging.

Answer 14

N0 - no spread
N1 - spread to 1-3 regional lymph nodes
N2 - spread to 4 or more regional lymph nodes

Question 15

Describe the M stage of colorectal cancer staging.

Answer 15

M0 - no metastatic spread (other than regional lymph nodes)

M1 - metastatic spread

Question 16

Describe the Duke’s staging criteria.

Answer 16

A - direct invasion only, but no extension beyond muscularis propria (T1/2, N0, M0)
B - direct invasion only, extending beyond muscularis propria (T3 or 4, N0, M0)
C - involvment of regional lymph ndoes, but no distant mets (N1 or 2, M0)
D - distant mets (M1)

Question 17

What is the purpose of Duke’s staging?

Answer 17

Duke’s A and B have a far better prognosis, so aren’t exposed to the toxic side effects of chemotherapy (offered to Duke’s C)

Question 18

How are colorectal cancers detected early?

Answer 18

Screening colonoscopy of ulcerative colitis patients
Bowel cancer screening programme
- testing of 50-75yr olds
- if positive, given colonoscopy 
Patient education of symptoms
- PR bleeding
- change in bowel habit

Question 19

What is a neuroendocrine tumour?

Answer 19

Neoplasm that arises from the cells of the endocrine and nervous system

Question 20

Where are neuroendocrine tumours normally found?

Answer 20

Appendix
- usually well-differentiated (benign) at this site
If found elsewhere, they tend to be more aggressive

Question 21

Describe the endocrine tumour categorisation.

Answer 21

Well differentiated (benign behaviour) endocrine tumour
Well differentiated (uncertain behaviour) endocrine tumour
Well differentiated endocrine carcinoma (low grade malignancy)
Poorly differentiated endocrine carcinoma (high grade malignancy)

Question 22

What does a neuroendocrine tumour look like on histology?

Answer 22

Composed of nest cells

- stain positively with immunocytochemistry antigens of neuroendocrine differentiation

Question 23

What is a gastrointestinal stromal tumour (GIST)?

Answer 23

Spindle cell tumour derived from the interstitial cells of Cajal
- more commonly arises in the upper GI tract than the lower

Question 24

What is the treatment for a GIST?

Answer 24

Imatinib (a tyrosine kinase inhibitor)

- because most have abnormalities of the TKR

Question 25

How can you tell if the treatment for GIST will work?

Answer 25

c-kit stain identifies upregulation of TKRs and predicts drugs response

Question 26

What is the most common lymphoma to occur in the intestine?

Answer 26

Enteropathy associated T cell lymphoma

- small bowel

Question 27

Which conditions increase the risk of enteropathy associated T cell lymphoma arising?

Answer 27

Untreated/refractory coeliac disease
- results in over stimulation of T-cells
- leads to higher risk of malignant transformation
Refractory sprue

Question 28

What is the histology of enteropathy associated T cell lymphoma?

Answer 28

Sheets of malignant lymphocytes replace normal mucosa

- eradicate glands