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131 Cards in this Set

  • Front
  • Back
What percent of the GI is the small intestine? What percent of tumors occur here?
- SI is 75% of length
- But only 3-6% of tumors are here
What are the most common tumors in the small intestine? Others?
- Most common: Adenoma (near ampulla)
- Others: carcinoid and adenocarcinoma have equal incidence
- Rare: mesenchymal tumors, lipoma, GIST, lymphoma
What does this specimen show?
What does this specimen show?
Tumors in small intestine by the Ampulla of Vader (cause back up of bile and pancreatic juices)
Tumors in small intestine by the Ampulla of Vader (cause back up of bile and pancreatic juices)
What are the risk factors for SI Adencarcinoma?
- Crohn’s disease
- Adenomas
- Celiac disease
- Familial polyposis syndrome
What is the most common non-epithelial (soft tissue) tumor in the GI tract?
Gastrointestinal Stromal Tumor (GIST)
Gastrointestinal Stromal Tumor (GIST)
What is the origin of the tissues in Gastrointestinal Stromal Tumor (GIST)?
Mesenchymal origin, derived from interstitial cells of Cajal (pacemaker cells)
Mesenchymal origin, derived from interstitial cells of Cajal (pacemaker cells)
What is Gastrointestinal Stromal Tumor (GIST) seen in?
- Carney triad
- Neurofibromatosis (no KIT or PDGFRA mutation)
- Carney-Stratakis syndrome (succinate dehydrogenase)
- Carney triad
- Neurofibromatosis (no KIT or PDGFRA mutation)
- Carney-Stratakis syndrome (succinate dehydrogenase)
What drug is clinically useful in Gastrointestinal Stromal Tumor (GIST)?
Gleevac (Imatinib)
Gleevac (Imatinib)
What kind of tumor is this?
What kind of tumor is this?
Gastrointestinal Stromal Tumor (GIST)
Gastrointestinal Stromal Tumor (GIST)
What are the most common locations of Gastrointestinal Stromal Tumors (GIST)?
- Stomach (60%)
- Small intestine (30%)
- Colon (4%)
- Stomach (60%)
- Small intestine (30%)
- Colon (4%)
What mutations are common in Gastrointestinal Stromal Tumor (GIST)?
- C-Kit mutations (80%)
- PDGFRA mutations (5-10%)
- C-Kit mutations (80%)
- PDGFRA mutations (5-10%)
What are the immunohistochemical identifications of Gastrointestinal Stromal Tumor (GIST)?
- CD117 (C-Kit) - positive in 90-100% of cases
- DOG1 - specific marker
- CD34 - positive in 85-95% of cases
- Muscle markers - actin (25%), desmin (10%), and S-100 (5%)
- CD117 (C-Kit) - positive in 90-100% of cases
- DOG1 - specific marker
- CD34 - positive in 85-95% of cases
- Muscle markers - actin (25%), desmin (10%), and S-100 (5%)
What are the microscopic identifications of Gastrointestinal Stromal Tumor (GIST)?
- Cells are EPITHELIOID
- More pleomorphic and with deeply acidophilic cytoplasm
- Features of smooth muscle differentiation (at immunohistochemical level - see markers of actin, desmin, and S-100)
- Cells are EPITHELIOID
- More pleomorphic and with deeply acidophilic cytoplasm
- Features of smooth muscle differentiation (at immunohistochemical level - see markers of actin, desmin, and S-100)
What are the immunohistochemical signs that are diagnostic for Gastrointestinal Stromal Tumor (GIST)?
- Few cells show c-KIT immunoreactivity, rendering a
diagnosis of gastrointestinal stromal tumor not that secure.
- Extensive positive staining for DOG1 supports the diagnosis
What kind of genes are c-kit (CD117) and PDGFRA?
Cell surface receptors - Tyrosine Kinase types
Cell surface receptors - Tyrosine Kinase types
What kind of tumor is a Carcinoid Tumor? What does that mean?
Neuroendocrine tumor:
- Secretes bioactive compounds (biogenic amines)
- Elevated serotonin (5-HT)
Neuroendocrine tumor:
- Secretes bioactive compounds (biogenic amines)
- Elevated serotonin (5-HT)
What are the signs of Carcinoid Syndrome?
- Vasomotor disturbances
- Intestinal hypermotility
- Wheezing
- Hepatomegaly
- Cardiac involvement
How does a Carcinoid Tumor present?
Submucosal nodule
Submucosal nodule
What does this slide show?
What does this slide show?
Submucosal Nodule - this is how Carcinoid Tumors present
Submucosal Nodule - this is how Carcinoid Tumors present
What do you see in MALT Lymphoma in the small intestine?
Colonization of the germinal centers by the tumor cells
Colonization of the germinal centers by the tumor cells
What is the term for an epithelium-derived tumor mass which protrudes into the gut lumen?
Polyp
What is a polyp? What are the types?
- Epithelium-derived tumor mass which protrudes into the gut lumen
- Pedunculated polyps
- Sessile polyps
- Epithelium-derived tumor mass which protrudes into the gut lumen
- Pedunculated polyps
- Sessile polyps
What is a non-neoplastic polyp the result of? Prognosis?
Abnormal mucosal maturation, inflammation, distorted architecture - no malignant potential
What is a neoplastic polyp the result of? Prognosis?
Arises as a result of proliferation and dysplasia (adenomas) - precursors of carcinoma
What is this?
What is this?
Pedunculated, Tubular Polyp
Pedunculated, Tubular Polyp
What is this?
What is this?
Sessile, Villous Polyp
Sessile, Villous Polyp
What kind of polyps are the result of abnormal mucosal maturation, inflammation, and distorted architecture? Types? Malignant potential?
Non-neoplastic polyps:
- Hamartomatous
- Inflammatory
- Lymphoid

No malignant potential
Hamartoma:
- Benign or malignant
- Structure
- Characteristics
- Cause
- Location
- Benign tumors
- Focal, mass of tissue resembling a tumor, pedunculated, 1-3 cm
- Composed of mature, histologically normal elements from a site that grow in a disorganized manner
- Due to developmental errors
- Occur in many sites (80% in rectum)
What kind of polyp is composed of mature, histologically normal elements that grow in a disorganized manner?
Hamartomas
What are the types of / syndromes with Hamartomatous Polyps?
- Juvenile Polyposis Syndrome
- Peutz-Jeghers Syndrome
- Cowden Syndrome
- Cronkhite-Canada
What is the cause of Hamartomas? Who gets them?
- Due to developmental error
- Juvenile: kids <5 years
What is the most common location of Hamartomatous polyps? Appearance / size?
- 80% occur in rectum
- Pedunculated, 1-3cm (this is large by polyp standards)
- 80% occur in rectum
- Pedunculated, 1-3cm (this is large by polyp standards)
What happens to the components of the mucosa in Hamartomatous Polyps?
- Expanded lamina propria with variable inflammation
- Lamina propria constitutes bulk of polyp
- Abundant, cystically dilated, tortuous glands
- Expanded lamina propria with variable inflammation
- Lamina propria constitutes bulk of polyp
- Abundant, cystically dilated, tortuous glands
What are the criteria of Juvenile Polyposis Syndrome? How is it inherited?
- Multiple juvenile hamartomatous polyps (>5, 50-100)
- Found in stomach, small intestine, colon, and/or rectum
- Increased risk of adenomas, 10-50% lifetime incidence of colon cancer, also gastric, small intestine, and pancreas
- Autosomal dom...
- Multiple juvenile hamartomatous polyps (>5, 50-100)
- Found in stomach, small intestine, colon, and/or rectum
- Increased risk of adenomas, 10-50% lifetime incidence of colon cancer, also gastric, small intestine, and pancreas
- Autosomal dominant
How is Juvenile Polyposis Syndrome inherited? What genes are abnormal? What are these patients at increased risk for?
Autosomal dominant:
- SMAD4 (20%)
- BMPR1A (20%)
- PTEN (0%)

Increased risk of adenomas
- 10-50% lifetime incidence of colon cancer
- Also gastric, small intestine, and pancreas
Autosomal dominant:
- SMAD4 (20%)
- BMPR1A (20%)
- PTEN (0%)

Increased risk of adenomas
- 10-50% lifetime incidence of colon cancer
- Also gastric, small intestine, and pancreas
What are the criteria of Peutz-Jeghers Syndrome? How is it inherited?
- Multiple Hamartomatous GI Peutz-Jeghers polyps (non-malignant)
- Hyperpigmentation: mucosal (mouth) and cutaneous (fingers)
- Large and pedunculated polyps containing CT and smooth muscle as well as abundant glands rich in Goblet cells
- Auto...
- Multiple Hamartomatous GI Peutz-Jeghers polyps (non-malignant)
- Hyperpigmentation: mucosal (mouth) and cutaneous (fingers)
- Large and pedunculated polyps containing CT and smooth muscle as well as abundant glands rich in Goblet cells
- Autosomal dominant: STK11
How is Peutz-Jeghers Syndrome inherited? What genes are abnormal? What are these patients at increased risk for?
Autosomal dominant:
- STK11

Increased risk of:
- Intussusception (inversion of one portion of the intestine within another)
- Cancer of pancreas, breast, lung, ovary, and uterus (50% lifetime risk of all types of cancer)
Autosomal dominant:
- STK11

Increased risk of:
- Intussusception (inversion of one portion of the intestine within another)
- Cancer of pancreas, breast, lung, ovary, and uterus (50% lifetime risk of all types of cancer)
What are the characteristics of Cowden Syndrome? How is it inherited?
- Hamartomatous GI polyps (non-malignant)
- Facial trichilemmomas, oral papillomas, acral keratoses
- Autosomal dominant
How is Cowden Syndrome inherited? What genes are abnormal? What are these patients at increased risk for?
Autsomal dominant

Increased risk of:
- Thyroid and breast cancer
What are the characteristics of Cronkhite-Canada? How is it inherited?
- GI hamartomatous polyps
- Ectodermal abnormalities (nail atrophy, alopecia)
- Non-hereditary
What are the other non-neoplastic polyps?
- Inflammatory polyps (pseudopolyps)
- Lymphoid polyps
What are the characteristics of inflammatory polyps?
- Non-neoplastic
- Pseudopolyps - regenerating mucosa adjacent to ulceration (severe IBD)
What are the characteristics of lymphoid polyps?
- Non-neoplastic
- Mucosal bumps
- Caused by intramucosal lymphoid follicles - normal
What are the types of Serrated Polyps?
- Hyperplastic Polyps
- Sessile Serrated Polyps
What are the smooth protrusions of mucosa usually at the tops of mucosal folds?
What are the smooth protrusions of mucosa usually at the tops of mucosal folds?
Serrated Polyps
Serrated Polyps
What is the most common location of Serrated Polyps?
Over half are found in the rectosigmoid colon
What is the histological appearance of Serrated Polyps?
Serrated lumina with increased numbers of goblet cells
Serrated lumina with increased numbers of goblet cells
What is the size of Serrated Polyps?
Very small - less than 5 mm in diameter
Very small - less than 5 mm in diameter
What kind of polyp is this? Location? Malignant potential?
What kind of polyp is this? Location? Malignant potential?
Hyperplastic Serrated Polyp
- 60-90% of serrated polyps
- Distal colon
- No malignant potential
Hyperplastic Serrated Polyp
- 60-90% of serrated polyps
- Distal colon
- No malignant potential
What kind of polyp is this? Location? Malignant potential?
What kind of polyp is this? Location? Malignant potential?
Sessile Serrated Polyp
- 10-30% of serrated polyps
- Proximal colon
- High malignant potential
Sessile Serrated Polyp
- 10-30% of serrated polyps
- Proximal colon
- High malignant potential
What kind of mutations are seen in Serrated Polyps?
- Hyperplastic: none discussed
- Sessile Serrated: BRAF V600E mutations
What is the progression of polyps to cancer?
Benign
1. Starts as hyper-proliferation
2. Grows into small and large adenomatous polyps
3. Leads to severe dysplasia (pre-cancerous polyp)

Malignant
4. Continues to grow into adenocarcinoma
5. Cancer progresses deep into tissues
Benign
1. Starts as hyper-proliferation
2. Grows into small and large adenomatous polyps
3. Leads to severe dysplasia (pre-cancerous polyp)

Malignant
4. Continues to grow into adenocarcinoma
5. Cancer progresses deep into tissues
What do Adenomatous Polyps (Adenomas) arise from?
As a result of epithelial proliferative dysplasia
As a result of epithelial proliferative dysplasia
What can Adenomatous Polyps progress to?
Precursor lesion for adenocarcinoma (4x greater risk if you have adenomatous polyps)
Precursor lesion for adenocarcinoma (4x greater risk if you have adenomatous polyps)
How common are Adenomatous Polyps? Who is at greatest risk?
- Common: 40-50% after age 60 (20-30% before age 40)
- 4x greater risk if you have 1st degree relative with adenomas
- 4x greater risk of carcinoma if you have adenoma
- M = F
What are the types of Adenomatous Polyps?
1. Tubular Adenoma
2. Villous Adenoma
3. Tubulovillous Adenoma
What is the morphological appearance of Tubular Adenomas? Location?
- Tubular glands
- Often small, pedunculated
- Can be single or multiple
- Rarely >2.5 cm
- Dysplastic epithelium - elongated, pseudostratified, hyperchromatic nuclei, w/ loss of mucin production

- 90% found in colon
- Tubular glands
- Often small, pedunculated
- Can be single or multiple
- Rarely >2.5 cm
- Dysplastic epithelium - elongated, pseudostratified, hyperchromatic nuclei, w/ loss of mucin production

- 90% found in colon
What is the morphological appearance of Villous Adenomas? Location?
- Villous projections
- Often large and sessile
- Up to 10 cm in diameter

- Most common in older people in rectosigmoid colon
- Villous projections
- Often large and sessile
- Up to 10 cm in diameter

- Most common in older people in rectosigmoid colon
When invasive carcinoma is present, what is the appearance of the Villous Adenoma? Where does invasion occur?
- When invasive carcinoma is present, there is no stalk to act as a buffer zone
- Cancer invasion occurs directly into the colon wall
- When invasive carcinoma is present, there is no stalk to act as a buffer zone
- Cancer invasion occurs directly into the colon wall
When is the cancer risk rare in Adenomas?
Tubular Adenomas < 1 cm
Tubular Adenomas < 1 cm
When is the cancer risk increased in Adenomas?
- 40% in patients with sessile, villous adenomas > 4cm
- High grade dysplasia is often found in the villous area
- High grade dysplasia or carcinoma can be found in any polyp
What are the symptoms of Adenomatous Polyps?
- May be asymptomatic
- May present with rectal bleeding or anemia
Where does intramucousal carcinoma invade? Metastatic potential?
Invades lamina propria - no metastatic potential
Where does invasive carcinoma in a pedunculated adenoma invade? Metastatic potential?
- Invades through muscularis mucosa
- Metastatic potential
How should you treat an invasive carcinoma in a pedunculated adenoma?
Endoscopic removal adequate if:
- Resection margins negative
- No vascular or lymphatic invasion
- Carcinoma is not poorly differentiated
How should you treat an invasive carcinoma in a sessile polyp?
Polypectomy inadequate, requires partial colectomy
How should you treat Adenomatous Polyps?
- Regardless of whether carcinoma is present, the ONLY ADEQUATE TREATMENT is COMPLETE RESECTION
- If adenomatous epithelium remains int he patient, there is potential for carcinoma
What is the most common type of Colorectal Cancer?
98% Adenocarcinoma (99% occur singly)
What is the prognosis of Colorectal Cancer? When is the peak incidence? Who is at increased risk?
- 9% of all cancer deaths in US
- 90% diagnosed at age 50+
- 1-3% occur in familial syndromes or IBD
What are the potential locations of Colorectal Cancer? How common in each location?
- Rectosigmoid colon (55%)
- Cecum and ascending colon (22%)
- Transverse colon (11%)
- Descending colon (6%)
- Rectosigmoid colon (55%)
- Cecum and ascending colon (22%)
- Transverse colon (11%)
- Descending colon (6%)
Where are the highest death rates from Colorectal Cancer?
- US
- Australia
- New Zealand
- Eastern Europe
What are the lifestyle risk factors for Colorectal Carcinoma?
Dietary practices:
- Excess dietary caloric intake
- Low fiber
- High content of refined carbohydrates
- Red meat
- Decreased intake of micronutrients

Obesity and physical inactivity
What are the clinical implications of right-sided Colon Cancer?
What are the clinical implications of right-sided Colon Cancer?
- Non-obstructive
- Fatigue, weakness
- Iron deficiency anemia
- Polypoid, exophytic lesions
- Non-obstructive
- Fatigue, weakness
- Iron deficiency anemia
- Polypoid, exophytic lesions
What are the clinical implications of left-sided Colon Cancer?
What are the clinical implications of left-sided Colon Cancer?
- May be obstructive
- Occult bleeding
- Changes in bowel habits
- Abdominal discomfort
- Annular "napkin ring" constrictions
- Tend to be more infiltrative
- May be obstructive
- Occult bleeding
- Changes in bowel habits
- Abdominal discomfort
- Annular "napkin ring" constrictions
- Tend to be more infiltrative
Colorectal carcinoma on what side is more severe, may be obstructive, and tends to be more infiltrative?
Left-sided lesions
Left-sided lesions
What is the most common clinical presentation of colorectal cancer?
- Asymptomatic for years w/ insidious onset
- Iron deficiency anemia in an older male signifies colon cancer unless proven otherwise
If you have an older male that is presenting with iron deficiency anemia, what do you suspect?
Colon cancer until proven otherwise
Colon cancer until proven otherwise
How do adenomas relate to colorectal cancer?
- Populations with a high prevalence of adenomas have a high prevalence of colorectal cancer, and vice versa
- Similar distribution of polyps and cancer in the colorectum
- Peak age for adenomas precedes peak age for cancer
- When cancer is identified at an early age, surrounding adenomatous tissue is often present
- Cancer risk directly related to number of adenomas
- Removal of polyps decreases cancer incidence
How can you decrease your risk of colorectal cancer?
Remove any adenomatous polyps
What can pretty much guarantee your development of colorectal cancer?
FAP Syndrome: Familial Adenomatous Polyposis
What is the molecular understanding of the adenoma-carcinoma relationship?
- Multi-hit hypothesis
- Accumulation of mutations is more important that the specific order of mutations
- Multi-hit hypothesis
- Accumulation of mutations is more important that the specific order of mutations
What molecular findings are associated with the adenoma-carcinoma pathway?
- >80% of colon cancers have inactivated APC
- 50% of cancers w/ APC mutations have β-catenin mutations (10% overall)
- Loss of p53 occurs late in colon carcinogenesis
- >80% of colon cancers have inactivated APC
- 50% of cancers w/ APC mutations have β-catenin mutations (10% overall)
- Loss of p53 occurs late in colon carcinogenesis
What are the implications of inactivated APC gene?
Dysfunction of APC leads to:
- Increased WNT signaling
- Decreased cell adhesion
- Increased cellular proliferation

>80% of colon cancers have inactivated APC
What genetic change occurs late in colon carcinogenesis?
Loss of p53
What pattern of Colorectal Cancer is associated with Ulcerative Colitis?
Infiltrative Colorectal Cancer:
- Insidiously infiltrative
- Difficult to identify grossly
- Exceedingly aggressive
- Spreads at early stage in evolution
How can you grade the depth of invasion of Colorectal Cancer?
- T(in situ / IS) = just in mucosa
- T1 = invaded into submuocsa
- T2 = invaded into muscularis propria
- T3 = invaded through serosa
- T4 = invades other organs or structures
- T(in situ / IS) = just in mucosa
- T1 = invaded into submuocsa
- T2 = invaded into muscularis propria
- T3 = invaded through serosa
- T4 = invades other organs or structures
How can you grade the lymph node involvement of Colorectal Cancer?
- N0 = no LN metastasis
- N1 = metastasis in 1-3 LNs
- N2 = metastasis in 4+ LNs
How can you grade the metastasis of Colorectal Cancer?
- M0 = no distant metastasis
- M1 = distant metastasis
What does a Stage 0 colon carcinoma indicate?
In situ carcinoma (tumor has not spread past the mucosa)
In situ carcinoma (tumor has not spread past the mucosa)
What does a Stage 1 colon carcinoma indicate?
- Tumor may have spread through submucosa (T1) or through muscularis propria (T2)
- No spread to lymph nodes or metastatic sites
- Tumor may have spread through submucosa (T1) or through muscularis propria (T2)
- No spread to lymph nodes or metastatic sites
What does a Stage 2 colon carcinoma indicate?
- Tumor may have spread through serosa (T3) or into adjacent structures/organs (T4)
- No spread to lymph nodes or metastatic sites
- Tumor may have spread through serosa (T3) or into adjacent structures/organs (T4)
- No spread to lymph nodes or metastatic sites
What does a Stage 3 colon carcinoma indicate?
- Tumor may have spread through any layer of the colon wall
- SPREAD TO LYMPH NODES
- No distant metastasis
- Tumor may have spread through any layer of the colon wall
- SPREAD TO LYMPH NODES
- No distant metastasis
What does a Stage 4 colon carcinoma indicate?
- Tumor may have spread through any layer of the colon wall
- Tumor may have spread to any number of lymph nodes
- DISTANT METASTASES
- Tumor may have spread through any layer of the colon wall
- Tumor may have spread to any number of lymph nodes
- DISTANT METASTASES
What is the most important prognostic indicator of colorectal carcinoma?
Extent of the tumor (stage) at the time of diagnosis
Extent of the tumor (stage) at the time of diagnosis
What is the prognosis for the different stages of Colorectal Cancer?
5-year survival:
- Stage 1: 93%
- Stage 2: 85%
- Stage 3: 70% - spread to lymph nodes
- Stage 4: 8% - distant metastasis
5-year survival:
- Stage 1: 93%
- Stage 2: 85%
- Stage 3: 70% - spread to lymph nodes
- Stage 4: 8% - distant metastasis
Where can Colon Cancer metastasize to?
- Direct extension into adjacent structures
- Spread to lymph nodes and vessels
- Goes to regional lymph nodes, liver, lungs, and bones
How common is metastatic spread of colon carcinoma upon presentation? Implications?
25-30% have metastasis (Stage 4) which indicates an 8% 5-year survival
What are the most common sites of metastasis of colon cancer?
- Liver
- Lungs
- Bones
- Liver
- Lungs
- Bones
What can we use to figure out the best therapy for a tumor and the prognosis of the cancer?
Prognostic and Predictive Biomarker Assessment (look at molecular features of tumor)
What is the utility of analyzing biomarkers on tumors?
Helps determine prognosis and best treatment (surgery, surgery + chemo, or best supportive care)
What are the traditional agents for treating Colorectal Cancer? Characteristics?
- 5FU / LV
- Capecitabine
- Irinotecan
- Oxaliplatin

- These cause all cells to die not just tumor cells; lots of side effects
What are the targeted agents for treating Colorectal Cancer? Characteristics?
- Bevacizumab
- Cetuximab
- Panitumumab

- These only harm tumor cells, thus have a lot less side effects
What are the kinds of biomarkers used to guide adjuvant therapy for colorectal cancer? Functions?
- Prognostic biomarkers - provide information about the patient's overall outcome, regardless of therapy (will it be more or less severe?)

- Predictive biomarkers - provide information about the effects of a particular therapeutic intervention (helps us figure out what drug to use)
What gene is important in Colorectal cancer?
EGFR (ErbB1 / Her1)
Activation of EGFR (ErbB1 / Her1) gene leads to what?
Stimulates key processes involved in tumor growth and progression:
- Proliferation
- Angiogenesis
- Invasion
- Metastasis
What 3 major pathways are activated when EGFR (ErbB1 / Her1) is activated?
- RAS-RAF-MAP kinase
- PI3K-AKT
- PLCγ
What is the structure of EGFR (ErbB1 / Her1)?
Transmembrane receptor with:
- Ligand binding domain (extracellular)
- Transmembrane domain
- Tyrosine kinase domain (intracellular)
Transmembrane receptor with:
- Ligand binding domain (extracellular)
- Transmembrane domain
- Tyrosine kinase domain (intracellular)
What drugs are being used to target EGFR (ErbB1 / Her1) = anti-EGFR?
- Cetuximab
- Panitumumab
What percent of Colorectal Cancer cases benefit from EGFR monoclonal Ab therapy (cetuximab and panitumumab)?
- Only 10-20% of cases benefit 
- Patients who do not respond have mutations in signaling pathway further down (thus blocking the EGFR receptor does nothing)
- Only 10-20% of cases benefit
- Patients who do not respond have mutations in signaling pathway further down (thus blocking the EGFR receptor does nothing)
What is the major negative predictor of efficacy in EGFR monoclonal Ab therapy? What other mutation correlates with poor prognosis and lack of response?
- KRAS mutation = major negative predictor
- BRAF mutation = poor prognosis and lack of response
- KRAS mutation = major negative predictor
- BRAF mutation = poor prognosis and lack of response
What are the hereditary syndromes involving the GI tract?
- Peutz-Jeghers, Cowden disease, and Juvenile polyposis
- Familial adenomatous polyposis (Gardner's syndrome and Turcot's syndrome)
- MYH Associated Polyposis (MAP)
- Lynch Syndrome / HNPCC (hereditary non-polyposis colorectal carcinoma syndrome)
How are the hereditary syndromes involving the GI tract inherited?
Usually autosomal dominant
Familial Adenomatous Polyposis:
- Inheritance pattern
- Number of lesions
- Presence of adenocarcinoma
- Treatment
- Other
- Autosomal dominant
- Typically 500-2500 colonic adenomas (minimum of 100)
- Colon adenocarcinoma occurs in ~100%
- Treat with prophylactic colectomy
- Autosomal dominant
- Typically 500-2500 colonic adenomas (minimum of 100)
- Colon adenocarcinoma occurs in ~100%
- Treat with prophylactic colectomy
What is this syndrome?
What is this syndrome?
Familial Adenomatous Polyposis:
- Autosomal dominant
- Typically 500-2500 colonic adenomas (minimum of 100)
- Colon adenocarcinoma occurs in ~100%
- Treat with prophylactic colectomy
Familial Adenomatous Polyposis:
- Autosomal dominant
- Typically 500-2500 colonic adenomas (minimum of 100)
- Colon adenocarcinoma occurs in ~100%
- Treat with prophylactic colectomy
What causes Familial Adenomatous Polyposis?
What causes Familial Adenomatous Polyposis?
- Inheritance (autosomal dominant) of germline mutation in the APC gene
- ~25% of FAP patients have no family history (new mutations in APC gene)
- Tumors result when the second normal allele is mutated in a cell during life ("somatic mutation")
- Inheritance (autosomal dominant) of germline mutation in the APC gene
- ~25% of FAP patients have no family history (new mutations in APC gene)
- Tumors result when the second normal allele is mutated in a cell during life ("somatic mutation")
What is the age of onset of polyps in Familial Adenomatous Polyposis? Onset of colorectal cancer?
What is the age of onset of polyps in Familial Adenomatous Polyposis? Onset of colorectal cancer?
Polyps:
- Median age 16 years
- Range 5-38 years
- Increasing number are detected with age

Colorectal Cancer:
- Late 30s, early 40s
Polyps:
- Median age 16 years
- Range 5-38 years
- Increasing number are detected with age

Colorectal Cancer:
- Late 30s, early 40s
What are the variants of Familial Adenomatous Polyposis?
- Attenuated FAP (<100 polyps)
- Gardner's syndrome
- Turcot syndrome
How does Attenuated Familial Adenomatous Polyposis differ from Classical FAP?
<100 polyps
<100 polyps
How does Gardner's Syndrome differ from Classical Familial Adenomatous Polyposis?
- Adenomatous polyposis with osteomas
- Epidermoid cysts
- Desmoid tumors
- Adenomatous polyposis with osteomas
- Epidermoid cysts
- Desmoid tumors
How does Turcot Syndrome differ from Classical Familial Adenomatous Polyposis?
Adenomatous polyposis with medulloblastoma
MYH Associated Polyposis (MAP):
- Inheritance pattern
- Number of lesions
- Other
- Autosomal recessive
- Typically 20-100 adenomatous polyps (can be >100)
- Phenotypic overlap with FAP (mostly attenuated FAP), but present at older age than for FAP
What causes MYH Associated Polyposis (MAP)?
- Mutations in MYH gene (1p34.3-p32.1) inherited in autosomal recessive pattern
- MYH protein is important for DNA repair (base excision repair and repairs oxidation induced DNA damage by removing A mis-paired with G)
- Mutations in MYH gene (1p34.3-p32.1) inherited in autosomal recessive pattern
- MYH protein is important for DNA repair (base excision repair and repairs oxidation induced DNA damage by removing A mis-paired with G)
What kind of cancer are patients with Lynch Syndrome at increased risk for?
- Colorectal Cancer
- Extra-Intestinal Cancer (endometrial cancer in females, also small intestine, ureter, and renal pelvis)
What happens in Lynch Syndrome / Hereditary Non-Polyposis Colorectal Cancer?
- Adenomas occur considerably earlier than in the normal population, but in low numbers
- Increased risk of colorectal cancer and extra-intestinal cancer (endometrial cancer in females, small intestine, ureter, and renal pelvis cancer too)
- Colonic carcinomas are often multiple and not necessarily associated with the adenomas
What is the cause of Lynch Syndrome / Hereditary Non-Polyposis Colorectal Cancer?
Genetic defect involves DNA mismatch repair genes (microsatellite instability pathway)
How long does it take an adenoma to progress to carcinoma in Lynch Syndrome / Hereditary Non-Polyposis Colorectal Cancer? Normally?
- Lynch syndrome: accelerated to 2-3 years
- Sporadic CRC: 8-10 years
How common is Lynch Syndrome in Colorectal Carcinoma patients?
1 in 35 have Lynch Syndrome
What is the risk for a second primary cancer in Lynch Syndrome?
16% in 10 years
What is the risk for new cancer in first/second degree relative of patient with Lynch syndrome?
35%-45% by age 70
What is a variant of Lynch Syndrome?
Muir-Torre Syndrome - associated with multiple sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas
What is the average age of presentation of the different types of cancer associated with Lynch Syndrome?
- Colon ~44 years
- Endometrial ~46 years
- Stomach ~56 years
- Ovarian ~43 years