SolidTumors-H&N,Thyroid,Skin,CNS

Question 1

Where is HPV-associated SCC usually found?

Answer 1

Oropharynx

• Base of tongue
• Tonsils

*70% of SCC in these sites are p16+

Question 2

Multiple Endocrine Neoplasia type I (MEN1; Wermer syndrome):

-Genetics/Chr

Answer 2

Germline MEN1 gene mutations

-Chr11

Question 3

MEN type I neoplasms. (7)

Answer 3

• Parathyroid Adenoma
• Pituitary Adenoma
• Pancreatic Islet Cell tumors
• Angiofibromas (facial)
• Collagenomas
• Lipomas
• Meningiomas

Question 4

MEN2A is AKA what?

Answer 4

Sipple syndrome

Question 5

MEN2A, MEN2B, and familial Medullary Thyroid Carcinoma (FMTC) are all caused by mutations in what gene/chromosome?

Answer 5

RET protooncogene

-chr10q

Question 6

MEN2A (Sipple syndrome) neoplasms. (3)

Answer 6

• Medullary carcinoma
• Pheochromocytoma
• Parathyroid adenoma

Question 7

MEN2A mutations involve what exons?

Answer 7

10 and 11

Question 8

MEN2B neoplasms/features. (5)

Answer 8

• Medullary carcinoma
• Pheochromocytomas
• Mucosal Neuromas
• Ganglioneuromatous GI polyps
• Marfinoid habitus

Question 9

MEN2B mutations involve what exon?

Answer 9

16

Question 10

Approximately 40% of sporadic Papillary Thyroid Carcinomas have somatic mutations in what gene?

Answer 10

RET

Question 11

What is the most common mutation in Papillary Thyroid Carcinoma?
-Variants %

Answer 11

BRAF V600E - Aggressive Behavior

• Conventional (60%)
• Tall Cell (80%)
• Follicular (10%)

Question 12

Mutations in BRAF, RET, and RAS are associated with PTC, all of these canuse what?

Answer 12

Unregulated MAPK stimulation

Question 13

Nearly all PTC with follicular architecture have what mutation?

Answer 13

RAS

Question 14

What is the most common mutation in cutaneous Melanoma that are NOT associated with sun damage?
-Responds to what treatment?

Answer 14

BRAF (pV600E predominantly)

-Inhibitor of BRAF kinase

Question 15

30% of melanomas are associated with what mutation?

-Responds to what treatment?

Answer 15

C-KIT

-TKI (Imatinib)

Question 16

DFSP translocation.

-Also seen in what?

Answer 16

COL1A1/PDGFB

-Pediatric Giant Cell Fibroblastoma

Question 17

Tumors acquiring what genetic anomalies differentiated into Astrocytomas?
-Oligodendrogliomas?

Answer 17

Astrocytomas:
-chr17p13 (TP53)

Oligos:
-1p/19q deletions

Question 18

Progression to grade IV glioma (secondary GBM) is usually marked by what?

Answer 18

Loss of 10q

Question 19

Primary GBM (not arising from low grade glioma) shows what genetic abnormalities? (3)

Answer 19

• EGFR amplification
• PTEN mutations
• 10q loss

Question 20

T/F: EGFR amplification and TP53 mutations often coexist in same tumor.

Answer 20

FALSE

-EGFR and TP53 mutations RARELY coexist

Question 21

Some GBMs show what genetic abnormality?

-Status of this profoundly impacts response to what?

Answer 21

MGMT gene silencing (promoter hypermethylation)
-Temozolamide/Radiotherapy

*Unsuppressed MGMT tumors are Resistant

Question 22

Mutation in what gene appears to be the sole inciting genetic event in Pilocytic Astrocytomas?

Answer 22

BRAF mutations (80%)

*Rare in diffuse astrocytomas

Question 23

Retinoblastoma gene/chr mutation?

Answer 23

RB1 gene on chr13

Question 24

Retinoblastoma inheritance.

Answer 24

90% sporadic

-10% ass. w/ germline defect in one copy of RB1 gene

Question 25

Patients with inherited mutations in RB1 are at high risk for later development of what neoplasms? (3)

Answer 25

• Osteosarcoma
• Pineal gland tumors
• Primitive Neuroectodermal Tumors (PNET)

Question 26

Meningioma genetic abnormality.

• Key region/Gene
• Protein encoded by gene

Answer 26

Monosomy of chr22

• 22q12.2 (NF2 gene)
• Merlin

Question 27

NF2 abnormalities are NOT typically seen in what subtype of meningiomas? (2)

Answer 27

• Meningothelial meningiomas (25%)

- Secretory meningiomas (<5%)

Question 28

Higher grade (atypical/anaplastic) meningiomas have additional complex anomalies, including numerous genetic gains and losses, what is the most common?

Answer 28

del 1p

Question 29

What syndromes are associated with a higher risk of Medulloblastoma? (3)

Answer 29

• Turcot syndrome (APC related)
• Gorlin syndrome
• Li-Fraumeni syndrome

Question 30

What are the common genetic abnormalities in sporadic medulloblastomas? (2)

Answer 30

• Isochromosome 17q (>50%)

- Loss of 17q (33%)

Question 31

Atypical Teratoid/Rhabdoid Tumor (AT/RT):

• gene/chromosome
• protein

Answer 31

Loss of SMARCB1 gene on chr22q11.2

-Encodes for INI1