Hereditary cancer syndromes

Question 1

VHL associated malignancies

Answer 1

• clear cell RCC
• Hemangioblastoma
• pheochromocytomas
• retinal angiomas

Question 2

Birt-hogg-dube syndrome gene mutation

Answer 2

folliculin (FLCN) gene

Question 3

Birt-hogg-dube syndrome associated malignancies

Answer 3

• clear cell RCC
• chromophobe RCC
• spontaneous PTX

Question 4

Tuberous sclerosis gene mutations

Answer 4

TSC1, TSC2

Question 5

Tuberous sclerosis associated malignancies

Answer 5

• clear cell RCC
• angiomyolipomas

Question 6

Hereditary papillary RCC gene mutation

Answer 6

CMET

Question 7

BAP1 associations

Answer 7

• clear cell RCC
• cutaneous and uveal melanoma
• mesothelioma (often peritoneal)

Question 8

Gene mutation and pathologies associated with hereditary paraganglioma and pheocromocytoma syndrome

Answer 8

succinate dehydrogenase
- clear cell RCC + pheochromocytomas

Question 9

MEN1 associated

Answer 9

3ps
pituitary adenomas
parathyroid adenomas
pancreatic islet cell tumors (VIPomas, Gastrinomas, insulinomas)
*Also carcinoid and adrenal tumors

Question 10

MEN2 mutations

Answer 10

RET mutations

Question 11

MEN2A malignancies

Answer 11

• medullary thyroid
• pheos
• primary parathyroid hyperplasia

Question 12

MEN2B

Answer 12

• medullary thyroid
• pheos
• mucosal neuromas

Question 13

MEN2B management

Answer 13

thyroidectomy before age 6
screen for pheos and hyperparathyroidism

Question 14

MUTYH polyposis associated malignancy

Answer 14

Increased risk of CRC

Question 15

Peutz jeghers syndrome gene mutation

Answer 15

STK11

Question 16

Peutz jeghers associated malignancies

Answer 16

• breast
• CRC
• gastric
• pancreatic
• ovarian
• lung
• *GI hamartomas
• mucutaneous pigmentation (SEE PHOTO online, will prob show photo)

Question 17

NF1 associated malignancies

Answer 17

• GIST
• peripheral nerve sheath tumors
• breast cancer

Question 18

PALB2 associated malignancies

Answer 18

• pancreatic
• Male breast cancer

Question 19

Which ovarian pts need germline testing?

Answer 19

universal

Question 20

Li fraumeni associated maligancies

Answer 20

• breast
• sarcoma
• brain tumors
• adrenocortical
• leukemia
• multiple primaries
• radiation induced malignancies
• aggressive prostate cancer

Question 21

Li fraumeni screening

Answer 21

• NO XRT
• MRI over CT to avoid radiation exposure
• Breast
• annual brain MRI
• ***annual whole body MRI annually
• endoscopy
• routine skin checks

Question 22

MSI pattern associated with hypermethylation pathway AND significance of BRAF in association

Answer 22

• loss of MLH1
• loss of PMS2
  *BRAF mutant indicates sporadic

Question 23

Lynch associated malignancies

Answer 23

• colon
• *endometrial
• ovarian
• prostate
• gastric
• small bowel
• CNS (glioma)
• bladder (UTUC)
• pancreatic
• sebaceous skin tumors
• rarely breast

Question 24

Lynch screening for colon and uterine

Answer 24

• colonoscopy q1-2 yrs starting at age 20-25
• salipingo-oophorectomy once child bearing complete

Question 25

FAP gene mutation

Answer 25

APC

Question 26

FAP associated malignancies

Answer 26

- early onset CRC - small bowel cancer - gastric - pancreatic - desmoid

Question 27

FAP mgmt

Answer 27

- annual c-scope starting at age 10-15 - total colectomy - CT or MRI looking at desmoid tumors

Question 28

BRCA1 chromosome

Answer 28

chromosome 17

Question 29

BRCA2 chromosome

Answer 29

chromosome 13

Question 30

BRCA subtype associated with higher risk of breast and ovarian and with TNBC

Answer 30

BRCA2

Question 31

BRCA2 other malignancies

Answer 31

- gastric - biliary - melanoma

Question 32

BRCA screening for breast cancer

Answer 32

- mammos starting at age 30 - MRI breast at age 25 - NO routine vaginal US or CA125

Question 33

BRCA2 mgmt for prostate cancer

Answer 33

- prostate cancer screening at age 40

Question 34

Cowden syndrome gene mutation

Answer 34

PTEN

Question 35

Cowden syndrome malignancies

Answer 35

- mucocutaneous lesions - macrocephaly - breast tumors - endometrial - thyroid - CRC - RCC - Melanoma

Question 36

Cowden syndrome screening

Answer 36

- MRI and mammos starting at age 30 - annual thyroid US starting at age 7 - Colonoscopy starting at age 35

Question 37

Alternative name for Lynch

Answer 37

Hereditary nonpolyposis colorectal cancer syndrome

Question 38

Gardner syndrome is a subtype of what disorder

Answer 38

FAP

Question 39

ATM associated malignancies

Answer 39

- pancreatic cancer - prostate cancer - stomach cancer - invasive ductal carcinoma of the breast

Question 40

Radiation in prostate cancer SE's

Answer 40

- bowel dysfunction - urinary frequency, incontinence, nocturia

Question 41

Radical prostatectomy in prostate cancer SE's

Answer 41

- urinary incontinence - *erectile dysfunction

Question 42

degarelix, relugolix mechanism

Answer 42

GnRH antagonists

Question 43

ADT duration for high risk disease

Answer 43

2 years

Question 44

Goserelin, triptorelin mechanism

Answer 44

GNHR/LHRH agonists

Question 45

Malignancy patients with fanconi anemia are at increased risk of

Answer 45

- head and neck cancer

Question 46

Answer to next step up after diagnosis of cancer in patient with Fanconi Anemia clinical features

Answer 46

- chromosome breakage test (severe toxicities from chemo)

Question 47

Additional screening required for CDKN2A mutant patients

Answer 47

MRCP + EUS for pancreatic cancer

Question 50

When germline testing is indicated for CRC

Answer 50

age <50

Question 51

High risk breast cancer screening - age + screening

Answer 51

Starting at age 30 - MRI and mammogram annually but staggered by 6 months so get imaging every 6 months

Question 52

Role of chemoprevention in high risk breast cancer patients

Answer 52

IF BRCA wildtype, tamoxifen IF BRCA1, no chemoprevention IF BRCA2, tamoxifen (reduces breast cancer by 50% but only prevents hormone receptor)

Question 53

Indications for germline testing in breast

Answer 53

Given metastatic disease OR triple negative any age OR diagnosis at age <50 OR multiple primary BC OR male OR Ashkenazi Jewish ancestry OR lobular with personal or FH h/o diffuse gastric OR >1 first degree relative with breast cancer <50/male breast/ovarian/pancreatic/high risk prostate OR >3 diagnosis of breast/prostate on same side of family (first and second degree) including the pt w/ breast cancer

Question 54

Screening required for FAP patients

Answer 54

- colonoscopy starting in teenage years - colectomy as polyps arise - Following colectomy, EGD - annual thyroid exams - annual abdominal exam for desmoid tumors

Question 55

CDH1 mutation 1) management 2) associated malignancies

Answer 55

Poppy sitting on steps/prostate cancer. CD’s all over floor/CDH1. Prophylactic gastrectomy recommended/T on the operating table in middle of room and surgeon cutting stomach out. BDSM chick with whip in front of doorway/autosomal dominant.

Question 56

CHEK2 associated malignancies

Answer 56

Coded character: Dr. Cerny Location: Josh’s room Scene: He has huge tits + gastric cancer patietn sitting at Josh’s desk + bill roebuck standing in wall + poppy + bones covering floor + Kathleen laying naked on floor /associated malignancies = breast + stomach + prostate + kidney + sarcoma + plasma cell neoplasms.

Question 57

Risk of ovarian cancer in BRCA1 and 2

Answer 57

1 = 40-60% (much higher) 2 = 13-29%

Question 58

Risk of contralateral breast cancer in BRCA1 and 2 pts

Answer 58

1 = 30-40% 2 = 25%

Question 59

RAD51c associated malignancies

Answer 59

Breast (especially triple negative) Ovarian

Question 60

RAD51c management

Answer 60

- annual mammo starting at age 40 - BSO at age 45