Tumors of the Bowel Flashcards
Familial adenomatous polyposis treatment options
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)
What is MYH polyposis
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.
Hereditary Non-Polyposis Colon Canacer
Most common inherited
Do no recommend prophylactic surgery
Two groups of HNPCC
- colorectal cancers only
2. colorectal and other cancers (endometrial…..
Clinical features of HNPCC
accelerated polyp-cancer sequence
Amsterdam Criteria for HNPCC 3-2-1 rule for considering HNPCC
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
Bethseda guidelines for HNPCC
- more involved way of screening for this disorder
Increase in sensitivity but decrease in specificity )nolonger just based on FMH)
immunohistochemistry screeing for mismatch repair genes in resected crc
MLH1, MSH2, MSH6, PmS2, –> positive is good. When proteins are not present, we worry about
Types of non-neoplastic polyps
- Hyperplastic, 2. Juvenile or Retention, 3. Peutz Jeghers
morphologic features of adenoma
mucin depletion
nuclei enlarged and different
–> low grade dysplasia
adenocarcinoma on histology
haphazard growth of glands
tubular adenoma
cells are crowded
have a high number of glandular/tubular compartments on low grade picture
Many nuclei –> look blue on H&E
mucin depleted
Villous adenoma
long villi which rise from the fibrovascular cores
they can carpet the mucosa in broad areas
- can lead to electrolyte disorders
Villous adenoma gross
carpeting of the villous adenoma - seen on endoscopy
tubullovillous adenoma
both glandular and villous components
- crowding, elongation and stratification of nuclei
loss of maturation seen as loss of mucin
low grade dysplasia
Treatment
excision of adenoma
- easier with pedunculated
Hyplastic polyp
hypermucinous lookk,
starfish appearance -
serration
—- appearance due to continued prolferation of cells - mature but do not slough so they need to accommodate themselves
juvenile
outline
inflamed lamina propia
difficult to distinguish from inflammatory polyps
Peutz-jeghers polyp
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.
colorectal adenocarcinoma
- Left-sided tumors (distal) tend to grow as annular, circumferential, ulcerated masses. So-called “napkin ring lesions”. Obstruction (change in bowel pattern) is common.
- 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.
STaging of CRC
no lymphoid vessels in mucosa –> so no lymph node metastases
those connected to lymph vessels = distant metastases
Forms of inherited Colorectal Cancer
Adenomatous Polyposis Syndromes: - FAP (Gardner’s; Turcot’s); MUTYH Polyposis Hamartomatous Polyposis Syndromes: - Peutz-Jeghers; Juvenile Polyposis Non-Polyposis Syndromes: - HNPCC (Lynch I & II)
FAP
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
Clinical Features of FAP
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
Ileo-anal puch advantages and disadvantages
Advantages= No permanent stoma Removes all mucosa? Preserves anal defecation Disadvantages= Multiple stages Higher morbidity Risk of pouch failure Requires good sphincter
MutHY Polyposis
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.
Epidemiology of MutHY Polyposis
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.
HNPCC
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
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
HNPCC
Types of Lynch
Lynch Syndrome 1 = Colorectal cancers only
Lynch Syndrome 2= Colorectal cancers; Other cancers (Endometrial, ovarian, pancreatic, gastric, small bowel, transitional cell of kidney/ureter)
Bethseda Guidelines for HNPCC
- 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
Diagnosis of Bethseda
Amsterdam I= 61% sensitivity
Amsterdam II = 72% sensitivity
Bethesda criteria = 94% sensitivity
Decreasing Specificity with increasing specifity
Juvenile or Retention Polyp
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
Pathologic Staging of Colon Adenocarcinoma
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.
Hyperplastic Polyp
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
Carcinoid Tumors malignant potential
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
Carcinoid Syndrome
Occurs in Pulmonic & tricuspid valve stenosis/regurge
