Tumors of the Bowel

Question 1

Familial adenomatous polyposis treatment options

Answer 1

Removal organ at risk:
- proctocolectomy with ileostomy –> best option
Other options with equivalent results in patients with milder sparing of rectum:
- colectomy with ileo-rectal anastomosis (spare rectum)
- restorative proctocolectomy with ileo-anal pouch (IPAA)

Question 2

What is MYH polyposis

Answer 2

Autosomal recessive polyposis…..
APC gene - susceptible to oxidative injuries that the mutY gene is supposed to repair.

Similar clinical presentation, risk of extra-colonic tumors, surgical options FAP.
Difference: Not quite as extensive disease as FAP. Risk of cancer is at a later age than FAP –> Proximal Colon.

Question 3

Hereditary Non-Polyposis Colon Canacer

Answer 3

Most common inherited

Do no recommend prophylactic surgery

Question 4

Two groups of HNPCC

Answer 4

1. colorectal cancers only

2. colorectal and other cancers (endometrial…..

Question 5

Clinical features of HNPCC

Answer 5

accelerated polyp-cancer sequence

Question 6

Amsterdam Criteria for HNPCC 3-2-1 rule for considering HNPCC

Answer 6

3 or more relatives with an HNPCC associated cancer (colorectal cancer, or cancer of the endometrium, small intestine, ureter or renal pelvis)

2 or more successive generations (1 should be a first-degree relative of the other two)

1 or more relatives diagnosed before the age of 50 years

Question 7

Bethseda guidelines for HNPCC

Answer 7

• more involved way of screening for this disorder

Increase in sensitivity but decrease in specificity )nolonger just based on FMH)

Question 8

immunohistochemistry screeing for mismatch repair genes in resected crc

Answer 8

MLH1, MSH2, MSH6, PmS2, –> positive is good. When proteins are not present, we worry about

Question 9

Types of non-neoplastic polyps

Answer 9

1. Hyperplastic, 2. Juvenile or Retention, 3. Peutz Jeghers

Question 10

morphologic features of adenoma

Answer 10

mucin depletion
nuclei enlarged and different
–> low grade dysplasia

Question 11

adenocarcinoma on histology

Answer 11

haphazard growth of glands

Question 12

tubular adenoma

Answer 12

cells are crowded
have a high number of glandular/tubular compartments on low grade picture
Many nuclei –> look blue on H&E
mucin depleted

Question 13

Villous adenoma

Answer 13

long villi which rise from the fibrovascular cores
they can carpet the mucosa in broad areas
- can lead to electrolyte disorders

Question 14

Villous adenoma gross

Answer 14

carpeting of the villous adenoma - seen on endoscopy

Question 15

tubullovillous adenoma

Answer 15

both glandular and villous components
- crowding, elongation and stratification of nuclei
loss of maturation seen as loss of mucin
low grade dysplasia

Question 16

Treatment

Answer 16

excision of adenoma

- easier with pedunculated

Question 17

Hyplastic polyp

Answer 17

hypermucinous lookk,
starfish appearance -
serration
—- appearance due to continued prolferation of cells - mature but do not slough so they need to accommodate themselves

Question 18

juvenile

Answer 18

outline
inflamed lamina propia
difficult to distinguish from inflammatory polyps

Question 19

Peutz-jeghers polyp

Answer 19

Non-neoplastic
Hamartomatous
Branching smooth muscle and glands lined by goblet cells
Slight malignant potential (LOH at LKB1 locus)
PJS pts at increased risk of developing CA of pancreas, breast, lung, ovary, and uterus.

Question 20

colorectal adenocarcinoma

Answer 20

1. Left-sided tumors (distal) tend to grow as annular, circumferential, ulcerated masses. So-called “napkin ring lesions”. Obstruction (change in bowel pattern) is common.
2. Right-sided tumors (proximal colon) tend to grow as polypoid, exophytic masses. May still be deeply infiltrating. Obstruction is uncommon. Occult bleeding (anemia) or melena.

Question 21

STaging of CRC

Answer 21

no lymphoid vessels in mucosa –> so no lymph node metastases
those connected to lymph vessels = distant metastases

Question 22

Forms of inherited Colorectal Cancer

Answer 22

Adenomatous Polyposis Syndromes:
- FAP (Gardner’s; Turcot’s); MUTYH Polyposis
Hamartomatous Polyposis Syndromes:
- Peutz-Jeghers; Juvenile Polyposis
Non-Polyposis Syndromes:
- HNPCC  (Lynch I & II)

Question 23

FAP

Answer 23

Autosomal dominant genetic disorder
Germline mutation in the APC gene 5q21
Diagnosis: >100 polyps in the colon and rectum
25% of probands have no family history

Question 24

Clinical Features of FAP

Answer 24

intestinal disease= by polyps present not only in the colon, but in the stomach and small intestine (duodenum).
extra-intestinal manifestations = desmoid tumors, osteomas, brain tumors, congenital hypertrophy of the retinal pigmented epithelium, hepatobiliary tumors, thyroid tumors, and adrenal tumors. Epidermoid cysts.
? Most common cause of death in FAP

Question 25

Ileo-anal puch advantages and disadvantages

Answer 25

``` Advantages= No permanent stoma Removes all mucosa? Preserves anal defecation Disadvantages= Multiple stages Higher morbidity Risk of pouch failure Requires good sphincter ```

Question 26

MutHY Polyposis

Answer 26

Autosomal recessive polyposis syndrome caused by bi-allelic germ line mutations in mutY homolog gene (base excision repair gene). Repairs oxidative DNA injuries. APC gene particularly prone to these injuries = may lead to somatic mutations in APC gene. Mono-allelic carriers -> no increased Ca risk. May have identical clinical presentation to FAP but generally pt’s have 15-100 adenomas. Mean age at cancer dx = 45 yrs. Not always accompanied by polyposis and may account for a proportion of patients with familial CRC.

Question 27

Epidemiology of MutHY Polyposis

Answer 27

66% of cancers occur in the ascending colon. Similar range of extracolonic tumors to those seen in FAP with addition of breast Ca. No established screening guidelines. Similar surgical options to those for FAP Consider MUTYH gene analysis in pts with FAP or AFAP w/ no APC gene abnormality.

Question 28

HNPCC

Answer 28

Most common inherited colon cancer syndrome. Autosomal dominant inheritance pattern. Germline mutation in mismatch repair genes (MMR): MSH2, MLH1, MSH6, PMS2. Lifetime risk of colorectal cancer = 60-80%. Originally, dx based on personal and family hx; clinically indistinguishable from sporadic CRC

Question 29

The precursor lesion is an adenomatous polyp, just as in sporadic CRC and clinical features may be indistinguishable from pts with sporadic CRC. Penetrance 40-60% therefore currently do not recommend prophylactic Rx

Answer 29

HNPCC

Question 30

Types of Lynch

Answer 30

Lynch Syndrome 1 = Colorectal cancers only Lynch Syndrome 2= Colorectal cancers; Other cancers (Endometrial, ovarian, pancreatic, gastric, small bowel, transitional cell of kidney/ureter)

Question 31

Bethseda Guidelines for HNPCC

Answer 31

- Colorectal carcinoma <50 years old - Synchronous or metachronous CRC or other Lynch syndrome-associated tumors, regardless of age - CRC with high microsatellite instability histology diagnosed in a patient less than 60 years old - CRC diagnosed in one or more first-degree relatives with a Lynch syndrome-associated tumor, with one of the cancers being diagnosed at less than 50 years of age - CRC diagnosed in two or more first-degree or second-degree relatives with Lynch syndrome-associated tumors, regardless of age

Question 32

Diagnosis of Bethseda

Answer 32

Amsterdam I= 61% sensitivity Amsterdam II = 72% sensitivity Bethesda criteria = 94% sensitivity Decreasing Specificity with increasing specifity

Question 33

Juvenile or Retention Polyp

Answer 33

Hamartomatous malformations Most frequent in the rectum Most often in children (<5yoa) Usually large (1 to 3 cm), round, smooth lesions with stalks Inflamed lamina propria with cystically dilated glands No malignant potential

Question 34

Pathologic Staging of Colon Adenocarcinoma

Answer 34

Carcinoma in situ (pTis) - Intraepithelial carcinoma (Severe dysplasia): No risk of metastasis - Intramucosal carcinoma = Limited to lamina propria: Very low risk of metastasis. Invasion into submucosa (pT1) Into muscularis propria (pT2) Through muscularis propria (pT3) Penetration of serosa or invasion of adjacent viscera (pT4) ***Increasing Risk of Mets as you Go Down.

Question 35

Hyperplastic Polyp

Answer 35

Small (usually <5 mm) sessile polyps Most common in the rectum/sigmoid Elongated and serrated, stellate crypts lined by “hypermature” goblet cells Do not have malignant potential

Question 36

Carcinoid Tumors malignant potential

Answer 36

All carcinoids are potentially malignant tumors. More likely benign depending on: (1) Site of origin = Appendiceal and rectal carcinoids usually benign (2) Depth of local penetration <2 cm) Intervention: Monitor Chromogranin A levels, urinary 5HIAA, Octreotide scans

Question 37

Carcinoid Syndrome

Answer 37

Occurs in Pulmonic & tricuspid valve stenosis/regurge