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Year 1 Material > Cancer Moffit Module > Flashcards

Cancer Moffit Module Flashcards

1
Q

What are the causes of hereditary colorectal cancer?

Causes of Hereditary Colorectal Cancer
A

Sporadic: (65% - 85%)
Rare Colorectal Cancer Syndromes: (<1.0%)
Familial Adenomatous Polyposis (FAP): (1%)
Hereditary Nonpolyposis Colorectal Cancer (HNPCC): (2% - 3%)
Familial: (10% - 30%)

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2
Q

What are the Risk Factors for Colorectal Cancer?

A
  • Age (median age ~71 years for USA)
  • Family Hx: ~2x increased risk if 1st degree relative (FDR) affected)
  • Inflammatory Bowel Disease (Ulcerative Colitis and Crohn’s disease)
  • Personal Hx of adenomatous polyps
  • Diet high in fat and/or low in fiber
  • Sedentary lifestyle and/or obesity
  • Smoking
  • Heavy alcohol use
  • Type II Diabetes
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3
Q

What genes are associated with Lynch Syndrome/ Hereditary Nonpolyposis Colorectal Cancer Syndrome (HNPCC)

A

MLH1

MSH2

MSH6

PMS2

EPCAM

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4
Q

What is the carrier frequency and risks associated with Lynch Syndrome?

A

General Population carrier frequency: 1/269 > More common in the general population than HBOC

Lifetime Risk of CRC: up to 82%

Lifetime risk of Endometrial/Uterine Cancer: Up to 60%

Additional increased cancer risks

Synchronous & metachronous CRC

7-18% of patients present with synchronous tumors

Presence of Extra-colonic cancers

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5
Q

What are the different Variants of Lynch Syndrome?

A

Muir-Torre Variant:

  • Lynch Syndrome + at least one sebaceous gland tumor (either an adenoma, an epithelioma, or a carcinoma)
  • The sebaceous gland tumors will commonly occur outside of the head and neck region
  • Most often due to mutations in the MSH2 gene, however can be due to mutations in MLH1

Turcot Variant:

-Associated with brain tumors, specifically glioblastoma

Constitutional Mismatch Repair Deficiency (CMMRD)
-Autosomal recessive condition very young age of onset of cancer development, risk for GI and hematologist malignancies, brain tumors, cafe-au-lait spots

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6
Q

Refer to NCCN guidelines for cancer risks

A
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7
Q

What are the pathological features of colorectal cancer that suggest Lynch Syndrome?

A
  • Tumor infiltrating lymphocytes
  • Crohn’s-like lymphocytic reaction
  • Mucinous OR signet-ring differentiation OR. Medullary growth pattern
  • Poorly differentiated
  • Location: right-sided CRC
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8
Q

Immunohistochemistry for the DNA Mismatch Repair Proteins

A
  • SCREENING TEST requires: Only tumor tissue
  • testing for protein expression in the tumor
  • sensitivity (true positive rate) in Lynch syndrome cases: 90%
  • Binding partners:o MLH1 & PMS2
    o MSH2 & MSH6
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9
Q

Bethesda Guidelines (BG) to identify colorectal tumors for MSI testing

A

-Originally (BG) issued in 1998

Revised Bethesda Guidelines, 2004

  1. CRC <50 years
  2. Synchronous or metachronous CRC or other Lynch Associated tumors*, regardless of ageex: Endometrial, gastric, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain, small intestinal tumors and sebaceous gland adenomas keratocanthomas
  3. CRC <60 years with MSI- high morphology**
    ex: Tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucinous/signet-ring differentiation, medullary growth pattern
  4. CRC in 1 or more First degree relative (FDR) with a Lynch-associated tumor, with one dx <50 years
  5. CRC in 2 or more FDR/second degree relative(s) (SDRs) w Lynch Associated tumors, regardless of age
    * Up to 50% of patients with Lynch syndrome do NOT meet revised Bethesda Guidelines (NCCN v2. 2017)
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10
Q

Microsatelite Instability

A
  • Sensitivity of MSI in Lynch syndrome cases: 90 - 95%
  • Requires both tumor tissue & normal tissue
  • MSI testing detects defects in the DNA mismatch repair process that lead to variation in size of nucleotide repeats that occur throughout the genome.
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11
Q

What are the different types of Immunohistochemistry (IHC)/MSI Testing Performed on Colon Tumor?

A
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12
Q

What are the different types of IHC/MSI Testing Performed on Uterine Tumor(s)?

A
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13
Q

NCCN Guidelines for tumor testing strategies (gene contingent)

A
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14
Q

What are the Amsterdam Criteria for Lynch Syndrome?

A

-First developed in order to identify families at risk for Lynch Syndrome

  • Original Amsterdam Criteria - 1991
    • At least 3 relatives with histology verified CRC
    • One should be a FDR to the other 2
    • At least 1 individual diagnosed with CRC under 50 years
  • FAP should be excluded
  • Revised Amsterdam Criteria - 1999 inclusion of endometrial cancer, small bowel, ureter or renal pelvis
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15
Q

What cancers are associated with Lynch Syndrome?

A
  • Colorectal
  • Endometrial
  • Gastric
  • Ovarian
  • Pancreatic
  • Urothelial
  • Brain (most often glioblastoma)
  • Biliary tract
  • Small intestine
  • Additional (skin): sebaceous adenomas, sebaceous carcinomas, keratoacanthomas- Muir Torre
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16
Q

Screening Recommendations for Lynch Syndrome? (Refer to NCCN guidelines)

A
17
Q

Growth cycle of a Polyp (picture)

A
18
Q

What are the two most important classifications of a polyp? (That we need to use medical records to verify?)

A
  • Number

- Subtype

19
Q

Histological Classification of Polyps

A

Epithelia Polyps

  • Arise from mucosal tissue (surface level)
  • Account for >95% of polyps

Hamartomatous Polyps

  • Arise form submucosal tissue
  • Accounts for <5% of polyps
20
Q

What is the difference between adenomatous polyps and hyperplastic polyps?

A
21
Q

Colon Polyp Pathway

A
22
Q

What conditions have Adenoma polyps?

A

Familial Adenomatous Polyposis
-Attenuated FAP

MYH-Associated Polyposis

23
Q

Familial Adenomatous Polyposis (FAP)

Inheritance?
De novo rate?
Characterization?
Penetrance?
Risk for CRC?
A
  • Characterized by the development of 100s to 1000s of colorectal adenomas
  • AD inheritance
  • 30% de novo rate

-Estimated penetrance for adenomas: 100%
Average age of polyp presentation = 16

  • Untreated polyposis leads to a virtually 100% risk for colon cancer
    • Average age of CRC diagnosis in untreated individuals w/ FAP = 39
24
Q

What are the Extracolonic Cancer Risks in FAP?

A
25
Q

What are the Extracolonic Features of FAP?

A
26
Q

What are Desmoids Tumors?

What are the independent risk factors for development?

A
  • Locally invasive, not malignant tumors
    • May still be deadly
  • Develop in ~10% of individuals w/ FAP
  • Pregnancy and/or Oral Contraceptive Pill(s) (OCP) may increase risk
  • Independent risk factors:
    • 3’ APC gene mutations
    • Family history
    • Females
    • Presence of osteomas
27
Q

Descriptions of Extracolonic Features

A
  • Congenital hypertrophy retinal pigment epithelium
    • Discrete, flat pigmented lesions of the retina
    • Do not cause clinical problems
    • Typically multiple and bilateral
  • Dental Anomalies
    • Extra Teeth, missing teeth, etc.
    • Discrete, flat pigmented lesions of the retina
    • Do not cause clinical problems
    • Typically multiple and bilateral
  • Osteomas
    • Bony overgrowths most often in the jaw and skull, not malignant
28
Q

What are the Variants of FAP?

What is the difference tween the Lynch Syndrome “T” and FAP “T”?

A

-Gardner “Syndrome”
FAP w/ extra intestinal lesions (desmoids, osteomas, dental anomalies, CHRPE, soft tissue tumors)

-Turcot
FAP w/ the presence of Medulloblastoma

*Turcot variant w/ Lynch Syndrome = association w/ Glioblastoma

29
Q

What is Attenuated FAP (AFAP)?

A
  • mutations in APC, however associated with a milder adenoma polyp burden
  • Later age of CRC onset (~50yrs)
  • Can also have Extracolonic features
30
Q

What is the difference between FAP and AFAP?

A
31
Q

What is the APC I1307K allele variant?

A

Year 1 Material (1 decks)

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