Intestinal Neoplasia Flashcards
What type of cancer are most colorectal cancers?
Adenocarcinomas (carcinomas of glandular origin) arising from the glandular epithelium which lines the mucosa
List some of the possible types of colorectal cancer.
Adenocarcinoma Small cell carcinoma Sqaumous cell carcinoma Metastatic carcinoma (mucosal or serosal deposits) Adenosquamous carcinoma Undifferentiated carcinoma Endocrine tumour Mixed carcinoid-adenocarcinoma Lymphoma
What is dysplasia?
Development of non-malignant cellular abnormalities
- small amount of genetic change increases risk of becoming malignant
What are colonic adenomas?
Dysplastic, benign, glandular neoplasms
Most as polyps
What does cribiform mean, and how can it relate to colonic neoplasms?
Cribiform - something is pierced by lots of holes
Hyperplasia of cells into adenomas/adenocarcinomas can have bad architecture and cribiform areas
What are the differential diagnoses of an adenoma?
Hyperplastic (metasplatic) polyps
Haemartomatous polyps
Inflammatory polyps
Submucosal lesions (e.g. lipoma or leiomyoma)
What are the risk factors for developing colorectal carcinoma?
Adenoma - size (>2cm) and number IBD - mainly ulcerative colitis Family history Other carcinomas - cancer from epithelial cells Polyposis syndromes
When should you be worried about malignancy with a benign polyp?
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
What is familial adenomatous polyposis?
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
Describe the pathophysiology associated with APC gene mutation.
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
What is Lynch Syndrome?
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)
How does Lynch syndrome lead to colonic carcinoma?
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
Describe the T stage when staging colonic carcinoma’s.
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
Describe the N stages of colorectal cancer staging.
N0 - no spread
N1 - spread to 1-3 regional lymph nodes
N2 - spread to 4 or more regional lymph nodes
Describe the M stage of colorectal cancer staging.
M0 - no metastatic spread (other than regional lymph nodes)
M1 - metastatic spread
Describe the Duke’s staging criteria.
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)
What is the purpose of Duke’s staging?
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)
How are colorectal cancers detected early?
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
What is a neuroendocrine tumour?
Neoplasm that arises from the cells of the endocrine and nervous system
Where are neuroendocrine tumours normally found?
Appendix
- usually well-differentiated (benign) at this site
If found elsewhere, they tend to be more aggressive
Describe the endocrine tumour categorisation.
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)
What does a neuroendocrine tumour look like on histology?
Composed of nest cells
- stain positively with immunocytochemistry antigens of neuroendocrine differentiation
What is a gastrointestinal stromal tumour (GIST)?
Spindle cell tumour derived from the interstitial cells of Cajal
- more commonly arises in the upper GI tract than the lower
What is the treatment for a GIST?
Imatinib (a tyrosine kinase inhibitor)
- because most have abnormalities of the TKR
How can you tell if the treatment for GIST will work?
c-kit stain identifies upregulation of TKRs and predicts drugs response
What is the most common lymphoma to occur in the intestine?
Enteropathy associated T cell lymphoma
- small bowel
Which conditions increase the risk of enteropathy associated T cell lymphoma arising?
Untreated/refractory coeliac disease
- results in over stimulation of T-cells
- leads to higher risk of malignant transformation
Refractory sprue
What is the histology of enteropathy associated T cell lymphoma?
Sheets of malignant lymphocytes replace normal mucosa
- eradicate glands
