Colorectal cancer Flashcards
What may be seen in colorectal cancer
Raised rolled edges, central ulcerated area
Summarise colorectal cancer
Major Cancer in ‘developed’ countries
4th most common cancer overall
2 leading cause of cancer death overall, behind lung cancer
Environmental (diet) and genetic factors in aetiology
Describe the basic anatomy of the colon
Front of colon lined by peritoneum
Back of colon- most lined by mesentery- with blood vessels
Rectum – completely covered by fatty tissue – no peritoneum
What type of carcinoma are most colon cancers
Adenocarcinoma
Describe the functions of the colon
What does the colon do? Extraction of water from faeces (electrolyte balance) Faecal reservoir (evolutionary advantage) Bacterial digestion for vitamins (e.g. B and K)
Faceal reservioir- don’t want to be defacating all the time- also prevents predators from tracing you
Describe the histology of colon
Epithelial layer and lamina propria-mucosa Muscularis mucosa Sub-mucosa Muscularis propria- thicker Fat and blood vessels- mesentery
Describe colonic anatomy
The colon is divided into:
the caecum which includes the ileocaecal valve and appendix
ascending (“right”) colon
the transverse colon
descending (left) colon
sigmoid colon and
rectum
The hepatic flexure is at the junction of the ascending and transverse colon while the splenic flexure is at the junction of transverse and descending colon. The rectum is below the level of the peritoneum surface ranging between 8-15 cm. in length.
Describe the importance of colon anatomy
The anatomy is important as the blood supply to these areas differs and also that colon cancers present in different ways when they arise in different parts of the colon. There is also evidence that there are some differences in molecular genetic abnormalities and behaviours in tumours arising in right side versus left side of the colon.
What are the crypts of liberkuhn
The colonic mucosal epithelium, from which carcinomas arise, consists of tubular crypts (of Lieberkuhn) lined by predominantly mucin secreting cells with intervening surface cells which are mainly absorptive cells. The absorptive cells have basally located nuclei and do not secret mucin, whereas in the crypts goblet cells synthesise and secrete mucin. Each crypt has 5-10 enteroendocrine cells (neuroendocrine cells) and a few stem cells. Occasional Paneth cells are seen in the base of the crypts of the caecum and ascending colon.
Describe the organisation of the colorectal mucosa
Columnar epithelial cells- basal nucleus- polarity occasional goblet cells stem cells at the bottom differentiate as they go up proliferate upwards endocrine cells mesenchyme cells
Red granules- endocrine cells
Describe the important of mucin production
Mucins involved in lubrication of the GI tract, frontline innate host defense
Goblet cells- mucin- increase lubrication to allow transit, immunological role too
Support cells- mesenchymal cells
Describe turnover of colon cells
2-5 million cells die per minute in the colon!
Proliferation renders cells vulnerable
APC mutation prevents cell loss mutation
Normally we have protective mechanisms to eliminate genetically defective cells by;
Natural loss
DNA monitors
Repair enzymes
Describe the significance of the high turnover rate of the colorectal mucosa
APC regulates a number of cellular functions including mitosis, migration and maintenance of genome stability.
High turnover- more likely for mutations to occur
Loss of cells – protects against cancer, DNA checkoiints and repair genes also play a role
Turnover:
o 2-5m cells per minute die in the colon high proliferation rate (cells are vulnerable to mutation).
o APC mutation PREVENTS cell loss and causes cell proliferation.
Normal protective mechanisms include – natural loss, DNA monitors & repair enzymes
What is the difference between polyps and adenomas
A polyp is any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous, etc
An adenoma is a benign neoplasm of the mucosal epithelial cells
Describe the colonic polyp types
Metaplastic/Hyperplastic Adenomas Juvenile Peutz Jeghers Lipomas Others (essentially any circumscribed intramucosal lesions)
Peutz jehgers- mucosal hyperpigmentation- higher risk of polyps
Describe hyper plastic polyps
Very common <0.5 cm 90% of all LI polyps Often multiple No malignant potential 15% have k-ras mutation
Describe the histological appearance of hyper plastic polyps
Fig. 11.202 Microscopic appearance of hyperplastic polyp. The individual glands show a typical serration of their mid portion.
Serrated appearance- due to hyperplastic overgrowth
Describe the different types of colonic adenomas
Tubular (>75% tubular) 90% Tubulovillous (25- 50% villous) 10% Villous ( > 50% villous) (Flat) (Serrated) The more villous, the worse.
Summarise adenomas
Colonic adenomas are very common lesions and increase with age. Most adenomas present in the 30-60 year age group and may be incidental findings at colonoscopy or cause symptoms by bleeding. They range in size from very tiny to large masses which can obstruct the colon.
Sometimes gastroenterologists see colonic lesions and describe them as polyps, but the term polyp is just applied to a mass lesion in the bowel which may or may not have a stalk. There are many different types of polyp, most of which are benign, and most are not adenomas. The majority of small colonic polyps are benign so called hyperplastic polyps. A minority are adenomas which are true neoplasms with genetic abnormalities.
Up to the age of 60 almost half of the population may be harbouring a small adenomatous polyp. There is a greater risk of developing polyps if you have first-degree relatives with colorectal carcinoma or adenomas, particularly if they are multiple.
Describe the anatomy of adenomas
Figure 3-20. Diagrammatic representation of carcinoma within a polyp. Black wedges represent foci of carcinoma. A wedges indicate carcinoma in situ; malignant cells do not traverse the muscularis mucosae. B wedges indicate invasive carcinoma; malignant cells have breached the muscularis mucosae.
Anatomy of the adenoma:
o Adenomas on a stalk – pedunculated.
o Flat and raised adenoma – sessile.
Can both be tubular, villous, etc.
Describe the microscopic structure of tubular adenomas
Tubular
Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
Increased proliferative activity
Reduced differentiation
Complexity/disorganisation of architecture
Purple- more nuclear material- also look larger
Nuceli lose paolarit- migrate to apical side
Describe the microscopic structure of villous adenomas
Villous
Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
Exophytic, frond-like extensions
Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia
Hypokalaemia due to mucin production- lose potassium into G.I tracts
Elongated nucleis
Increased nuclear:cutoplasmic ratio
What is an important difference between tubular and villous adenomas
The important features are that tubular adenomas are often well defined and pedundulated and whereas villous adenomas are often larger, more diffuse (‘carpet papillomas’) and difficult to sample in the centre where carcinomas develop. Some very large villous adenomas more than 5 cm in diameter have a high risk of harbouring a cancer (more likely than not).
Describe dysplasia
Literal meaning ‘bad growth’ Abnormal growth of cells with some features of cancer C.f. atypia Subjective analysis Indefinite, low grade and high grade
Poorly differentiated
Cribiform architecture- massive nuclei
High grade
Summarise villous carcinomas
Fig. 11.199 Large villous adenoma with an ulcerated adenocarcinoma in its center. (Courtesy of Dr. Facchetti, Brescia, Italy).
Ulceratec core- adenocarcinoma
Describe adenomatous polyposis coli (APC/FAP)
5q21 gene mutation
Site of mutation determines clinical variants (classic, attenuated, Gardner, Turcot etc)*
Many patients have prophylactic colectomy<30
Gardner’s- bone lesions and tumours in skin
Turcot- brain tumours too- glioblastomas and medulloblastomas
Describe the key figures associated with colonic adenoma
25% of adults have adenomas at age 50
5% of these become cancers if left
Large polyps have higher risk than small ones (so 5% > 1 cm 50-60, 15% at 75)
Lead time 10years?
Cancers stay at a curable stage c. 2 years
Lead time- development of adenoma to development to adenocarcinoma
Screening programme- need to know antural history well
