Soft Tissue Tumors: Sarcoma Cytogenetics

Front 1

Ewing's sarcoma/PNET

Back 1

t(11;22)(q24;q12) FLI-1/EWSR1
- 95% cases
t(21;22)(q22;q12) ERG/EWSR1
- 5% cases
t(7;22)(p22;q12) ETV1/EWSR1
t(17;22)(q12;q12) EIAF/EWSR1
t(2;22)(q33;q12) FEV/EWSR1

Front 2

t(11;22)(q24;q12)

Back 2

Ewing's sarcoma/PNET
FLI-1/EWSR1

CONTRAST:
t(11;22)(p13;q12)
WT1/EWSR1
DSRCT

Front 3

t(17;22)

Back 3

t(17;22)
PDGFB/COL1A1

DFSP/GCFB

Front 4

Alveolar rhabdomyosarcoma

Back 4

t(2;13)(q35;q14) PAX3/FOXO1A or FKHR
- 95% cases(65% cases)

t(1;13)(p36;q14) PAX7/FOXO1A or FKHR
- 10% cases (15% cases)

CONTRAST:
Alveolar soft part sarcoma (ASPS)
t(X;17)(p11;q25)
ASPL/TFE3

Front 5

Myxoid/round cell liposarcoma

Back 5

t(12;16)(q13;q12) DDIT3/FUS or CHOP/TLS >95% cases

t(12;22)(q13;q11-12) CHOP/EWS

CONTRAST:
Clear cell sarcoma
t(12;22)(q13;q11-12) ATF1/EWS

Front 6

desmoplastic small round cell tumor (DSRCT)

Back 6

t(11;22)(p13;q12)
WT1/EWSR1

Front 7

synovial sarcoma

Back 7

t(X;18)(p11.2;q11.2)
SSX1/SYT
SSX2/SYT

CONTRAST:
t(X;17)
ASPL/TFE3
Alveolar soft part sarcoma (ASPS)

Front 8

Clear cell sarcoma

Back 8

t(12:22)(q13;q12)
ATF1/EWSR1

CONTRAST:
t(12;22)(q13;q11-12)
Myxoid/round cell liposarcoma
CHOP(DDIT3)/EWSR1

Front 9

extraskeletal myxoid chondrosarcoma

Back 9

t(9;22)(q22;q12) 75% cases
NR4A3/EWSR1 or CHN/EWS
t(9;17)(q22;q11) 25% cases
NR4A3/RBP56 or CHN/TAF2N

CONTRAS:
t(9;22)(q34;q11)
BCR/ABL
CML

Front 10

DFSP/giant cell fibroblastoma

Back 10

t(17;22)(q22;q13)
PDGFB/COL1A1

Front 11

infantile fibrosarcoma

Back 11

t(12;15)(p13;q25)
ETV6/NTRK3
>95%

Front 12

alveolar soft part sarcoma

Back 12

t(X;17)(p11;q25)
ASPL/TFE3

Front 13

low grade fibromyxoid sarcoma

Back 13

t(7;16)(q33;p11)
FUS/CREB3L2

Front 14

angiomatoid MFH is associated with rearrangements of __

Back 14

ATF1

Front 15

aytpical lipomatous tumor/WD liposarcoma

Back 15

ring 12q and giant marker chromosome

Front 16

lipomas are associated with rearrangements involving

Back 16

12q15

6p21

Front 17

lipoblastomas are associated with rearrangments involving

Back 17

8q11-13

Front 18

aytpical lipomatous tumor/WD liposarcoma is associated with ___ of genes on chromosome __; the genes include:

Back 18

amplification

12q13-15

HMG1C
MDM2
SAS
CDK4

Front 19

endometrial stroma sarcoma is associated with translocation __

Back 19

t(7;17)(p15;q21)

Front 20

extrarenal rhabdoid tumor is associated with deletion or rearrangements of __

Back 20

22q11.2

Front 21

Most common cytogenetic abnormalities seen in single lipomas:

Back 21

- translocations involving 12q13-15

- rearrangements of 13q

- rearrangements of 6p21-33

Front 22

cytogenetic abnormalities associated with angiolipoma

Back 22

NONE!! unique

normal karyotype

Front 23

cytogenetic abnormalities associated with pleomorphic liposarcoma

Back 23

complex rearrangements

Front 24

EWS-ATF1
EWS-WT1
EWS-NR4A3
EWS-FLI1
EWS-CHOP(DDIT3)

Back 24

EWS-ATF1 t(12;22)
-- clear cell sarcoma
EWS-WT1 t(11;22)(p13;q12
-- DSRCT
EWS-NR4A3 t(9:22)
-- extraskeletal myxoid chondrosarcoma
EWS-FLI1 t(11;22)(q24;q12)
-- EWS/PNET
EWS-CHOP(DDIT3) t(12;22)
-- <5% of myxoid liposarc

Front 25

nomenclature used to describe human genes:
- official name assigned by HUGO
- common names

Back 25

- HUGO (Human Gene Nomenclature Committee)

Front 26

Ewing Sarcoma/PNET: EWS(EWSR1)-FLI1 fusion involves the ___-terminal domain of EWS

Back 26

- amino terminal domain (N-terminal portion) of EWS and the C-termina portion of FLI1

Front 27

Alveolar rhabdomyosarcoma (ARMS): translocations included __ and ___; testing for these make up the most commonly requested sarcoma translocation assays (why?)

Back 27

t(2;13) PAX3-FKHR (60-70%)

t(1;13) PAX7-FKHR (10-20%)

10-30% of ARMS lack either of these translocations

- morphologically, ARMS and embryonal rhabdomyosarcomas (ERMS) may be indistinguishable, and treatment is different (reason why this is the most commonly requested sarcoma translocation assay)

- PAX3-FKHR positive ARMS are more aggressive than PAX7-FKHR positive ARMS (however, they look identical)
-

Front 28

extraskeletal myxoid chondrosarcomas (EMC) harbor translocations involving ___, while skeletal myxoid chondrosarcomas __

Back 28

t(9;22)(q22;q12) NR4A3-EWS

- skeletal myxoid chondrosarcomas lack this fusion (supporting the fact that these represent distinct entities)

Front 29

Inflammatory myofibroblastic tumor can be positive by IHC for __ in __% of cases

Back 29

ALK up-regulation (60%)
- not specific for IMT, as other mesenchymal tumors may show ALK positivity
- ALK positivity in IMT is more common in children and less so in adults

Front 30

t(12;15) ETV6-NTRK3 is seen in ___

Back 30

infantile fibrosarcoma and congenital mesoblastic nephroma (kidney tumor)

- not seen in adult fibrosarcomas

- infantile fibrosarcomas have a better prognosis than adult types

Front 31

locally advanced and metastatic DFSP can be treated with __ due to ___

Back 31

- imatinib
- imatinib blocks the PDGFB signaling on which the tumor needs for cellular proliferation and survival

t(17;22) COL1A1-PDGFB fusion

Front 32

Giant cell tumor of tendon sheath and pigmented villonodular synovitis have been shown to be true neoplasms based on ___

Back 32

- finding recurrent t(1;2) CSF1-COL6A3 fusion in a significant number of GCTTS and PVNS

- leads to overexpression of CSF1, which is detected in the minority of intratumoral cells (only a minority of cells in GCTSS and PVNS are neoplastic - the others are recruited by the local overexpression of CSF1)

Front 33

KIT gene is on chr __

Back 33

4

Front 34

KIT receptor plays a normal role in ___

Back 34

- development and function of interstitial cells of Cajal (ICC)
- hematopoiesis
- gametogenesis
- melanogenesis

Front 35

1/3rd of GIST lackig KIT mutations harbor mutations in __

Back 35

PDFGA

Front 36

PDFGA-mutated GIST

Back 36

- preference for gastric location
- epithelioid morphology
- variable absence of KIT expression by IHC

Front 37

10% of GIST are ___ for both KIT and PDGFA

Back 37

negative
- in particular, pediatric GIST and GIST in NF-1 patients are almost always wild-type (not mutated) for both genes

Front 38

__% of GIST are KIT-negative by IHC

Back 38

4% are KIT-negative GIST
- more likely to be epithelioid
- contain PDGFA mutations
- arise extra-gastrointestinal locations

Front 39

patients with KIT-negative GIST (by IHC alone)should ___ offered tx w/ imatinib

Back 39

should be
- they may still have imatinib-sensitive KIT or PDGFA mutations

Front 40

Imatinib mesylate is a __

Back 40

selective tyrosine kinase inhibitor that targets KIT and PDGFA

- partial or stable disease in 80% of metastatic GIST cases

- complete and long-lasting responses are rare (50% develop resistance)