Sarcoma and mesenchymal tumors Flashcards by Stephen Babcock

Molecular features of sarcomas as a class

30% translocation-associated
70% complex karyotype

How well did you know this?

Not at all

Perfectly

Translocations in alveolar rhabdomyosarcoma

PAX3-FOXO1A - 75%
PAX7-FOXO1A - 20%
PAX3 with various partners (FOXO4, NCOA1, NCOA2, AFX) - 5%

How well did you know this?

Not at all

Perfectly

Translocations in alveolar soft part sarcoma

ASPSCR1-TFE3 - >95% of cases

How well did you know this?

Not at all

Perfectly

Translocations in angiomatoid fibrous histiocytoma

EWSR1-CREB1 72%
EWSR1-ATF1 21%
FUS-AFT1 7%
EWSR1-CREM Rare

How well did you know this?

Not at all

Perfectly

Molecular features in angiosarcoma, radiation associated

MYC amplification

How well did you know this?

Not at all

Perfectly

Molecular features in atypical lipomatous tumor / well differentiated liposarcoma

HMGIC, CDK4, and MDM2 amplification

How well did you know this?

Not at all

Perfectly

Translocations in biphenotypic sinonasal sarcoma

PAX3-MAML3 (most common)
PAX3-FOXO1
PAX3-NCOA1
PAX3-NCOA2
PAX3-WWTR1

How well did you know this?

Not at all

Perfectly

Translocations in clear cell sarcoma of soft parts

EWSR1-ATF1 - 90%
EWSR1-CREB1 - 10%
EWSR1-CREM - Rare

How well did you know this?

Not at all

Perfectly

Molecular features in clear cell sarcoma of the kidney

BCOR internal tandem duplications

Some overlap with renal sarcomas harboring BCOR-CCNB3 or YWAAE-NUTM2B

How well did you know this?

Not at all

Perfectly

Translocations in dermatofibrosarcoma protuberans

COL1A1-PDGFB - 95% of cases
Rarely other PDGFB partners

How well did you know this?

Not at all

Perfectly

Translocations in desmoplastic small round cell tumor

EWSR1-WT1 - >95% of cases

How well did you know this?

Not at all

Perfectly

Translocations in low grade endometrial stromal sarcoma

JAZF1-SUZ12
JAZF1-PHF1
JAZF1-BCORL1
EPC1-PHF1
MEAF6-PHF1
BRD8-PHF1
MBTD1-CXorf67

How well did you know this?

Not at all

Perfectly

Translocations in high grade endometrial stromal sarcoma

KDM2B-BREBBP
YWHAE-NUTM2B
ZC3H7B-BCOR

How well did you know this?

Not at all

Perfectly

Translocations in epithelioid hemandioendothelioma

WWTR1-CAMTA1 - 85% of cases
TFE3-YAP1

How well did you know this?

Not at all

Perfectly

Translocations in Ewing sarcoma and PNET/Ewing family of tumors

EWSR1-FLI1 (90%)
EWSR1-ERG (5%)
other EWSR1 partners: ETV1, ETV4, FEV, PATZ1, SP3, NFATC2, SMARCA5, POU5F1
FUS-ERG
FUS-FEV

How well did you know this?

Not at all

Perfectly

Translocations in extraskeletal myxoid chondrosarcoma

EWSR1-NR4A3 (75%)
TAF15-NR4A3 (15%)
TCF12-NR4A3
TFG-NR4A3
HSPA8-NR4A3
NR4A3-FUS

How well did you know this?

Not at all

Perfectly

Translocations in infantile fibrosarcoma

ETV6-NTRK3 (>95%)
EML4-NTRK3
BRAF fusions

How well did you know this?

Not at all

Perfectly

Translocations in uterine epithelioid leioyosarcoma

NRA4A3-PGR and other PGR rearrangements

How well did you know this?

Not at all

Perfectly

Translocations in uterine myxoid leiomyosarcomas

TRPS1-PLAG1
RAD51B-PLAG1

How well did you know this?

Not at all

Perfectly

Translocations in low-grade fibromyxoid sarcoma

FUS-CRE3L2 (>95%)
FUS-CREB3L1 (less than 5%)
EWSR1-CREB3L1

How well did you know this?

Not at all

Perfectly

Translocations in malignant tenosynovial giant cell tumor

CSF1-COL6A3

How well did you know this?

Not at all

Perfectly

Translocations in mesenchymal chondrosarcoma

HEY1-NCOA2 (>90%)

How well did you know this?

Not at all

Perfectly

Translocations in myoepithelial tumors of soft tissue

EWSR1-POU5F1
EWSR1-ZNF444
EWSR1-PBX1
EWSR1-PBX3
EWSR1-KLF17
EWSR1-ATF1

How well did you know this?

Not at all

Perfectly

Translocations in myxoid liposarcoma

FUS-DDIT3 (90%)
EWSR1-DDIT3 (10%)

How well did you know this?

Not at all

Perfectly

Translocations in myxoinflammatory fibroblastic sarcoma

TGFBR3-MGEA5

Translocations in ossifying fibromyxoid tumor

MEAF6-PHF1 EPC1-PHF1 EP400-PHF1 PHF1-TFE3 ZC3H7B-BCOR CREBBP-BCORL1 KDM2A-WWTR1

Translocations in perivascular epithelioid cell tumor (PEComa)

TSC2 mutation (unless TFE3 rearranged) PSF-**TFE3** DVL2-**TFE3** NONO-**TFE3** RBMX-**TFE3** RAD51B-RRAGB HTR4-ST3GALI RASSF1-PDZRN3 SCL4A10-**ROS1** **ROS1**-NETO1

Translocations in PRDM10-rearranged soft tissue tumor

CITED2-PRDM10 MED12-PRDM10

Translocations in pseudomyogenic hemangioendothelioma

SERPINE1-FOSB (50%) ACTB-FOSB (50%)

Translocations in primary pulmonary myxoid sarcoma

EWSR1-CREB1

Translocations in sclerosing epithelioid fibrosarcoma

EWSR1-CREB2L2 EWSR1-CREB2L1 RESR1-CREB3L3 FUS-CREB3L2

Translocations in solitary fibrous tumor

NAB2-STAT6 (>95%)

Translocations in spindle cell / sclerosing rhabdomyosarcoma

VGLL2-CITED2 NCOA2 fusions or MYOD1 L122R

Translocations in synovial sarcoma

SS18-SSX1 (65%) SS18-SSX2 (35%)

Translocations in undifferentiated small round cell sarcomas

CIC-DUX4 CIC-DUX4L CIC-FOXO4 CIC-NUTM1 NUTM2A-CIC BCOR-CCNB3 BCOR-MAML3 BCOR ITDs

Translocations in acral fibroblastic spindle cell neoplasm

EWSR1-SMAD3

Translocations in "aggressive" deep angiomyxoma

HMGA2 rearrangements

Translocations in angiofibroma of soft tissue

AHRR-NCOA2 GTF21-NCOA2 GAB1-ABL1 TBCK-PH4A2 PH4A2-TBCK NCOA2-ETV4 ETV4-AHRR

Translocations in aneurysmal bone cyst

USP6 translocations with multiple partners Most common is USP6-CDH11

Translocations in calcifying aponeurotic fibroma

FN1-EGF

Molecular alterations in chondroblastoma

H3F3B K36M

Translocations in chondromyxoid fibroma

COL12A1-GRM1 TBL1XR1-GRM1 BCLAF1-GRM1

Translocations in cutaneous non-neuronal granular cell tumor

SQSTM1-ALK DCTM1-ALK

Molecular alterations in desmoid tumors

Sporadic: CTNNB1 Germline: APC

Translocations in ectomesenchymal chondromyxoid tumor

RREB1-MKL2 EWSR1 rearrangements

Translocations in epithelioid fibrous histiocytoma

ALK fusions with various partners

Translocations in fibroma of tendon sheath

USP6 translocations

Translocations in fibro-osseous pseudotumor of the digits

USP6 translocations

Molecular alterations in fibrous hamartoma of infancy

EGFR ITDs

Translocations in gastroblastoma

MALAT1-GLI1

Molecular alterations in giant cell tumor of bone

H3F3A G34W or G34V rarely G34R or G34L

Translocations in lipoblastoma

PLAG1 rearrangements

Translocations in lipofibromatosis

HBEGF-RBM27 EGR1-GRIA1 TPR-ROS SPARC-PDGFRB VCL-RET EGFR-BRAF

Translocations in lipofibromatosis-like neural tumor

NTRK1-rearrangements

Translocations in lipoma

HMGA1 or HMGA2 rearrangements

Translocations in chondroid lipoma

C11orf95-MKL2

Molecular alterations in pleomorphic/spindle cell lipoma

RB1 loss

Translocations in cellular myofibroma

SRF-RELA

Molecular alterations in myopericytoma/myofibroma

PDGFRB mutations

Translocations in myositis ossificans

USP6 rearrangements

Molecular alterations in myxomas

GNAS activating mutations

Translocations in nodular fasciitis

MYH9-USP6 (most common) Other USP6 rearrangements

Translocations in pericytoma

ACTB-GLI1

Translocations in phosphaturic mesenchymal tumor

FN1-FGFR1

Translocations in plexiform fibromyxoma

MALAT1-GLI1

Translocations in osteoblastoma / osteoid osteoma

FOS and FOSB rearrangements

Molecular alterations in schwannoma

NF2 loss

Translocations in synovial chondromatosis

FN1-ACVR2A or ACVR2A-FN1 Present in both benign and malignant forms.

Translocations in tenosynovial giant cell tumor

CSF1-COL6A3

MDM2 amplified mesenchymal tumors

Defining molecular features of adipocytic neoplasms

Common molecular alterations in tumors of small vessels

Tend to have mutations in the Gaq family proteins (GNAQ, GNA11, GNA14). Hotspot mutations in these genes disrupt GTPase activity regulating the MAPK pathway.

Molecular alterations in vascular tumors

Tumors with EWSR1 fusion to a CREB family member (CREB1, CREM, ATF1)

NCOA2

Nuclear receptor co-activator-2 Transcriptional co-activator Interacts with ligand-bound receptors to recruit histone acetyltransferases and methyltransferases, facilitating chromatin remodeling. Frequent 3' fusion partner in mesenchymal neoplasms. The C-terminal transactivation domains 1 and 2 are retained in fusion proteins.

Tumors with NCOA2 fusions

Tumors with GLI1 fusions

GLI1

GLI1 is an effector of the sonic hedgehog pathway with multiple downstream targets.

Tumors with NTRK1/2/3 fusions

SMARCB1-deficient mesenchymal neoplasms

Tumors which bare the FUS-ERG translocation

Ewing sarcoma AML or ALL with t(16;21)

Tumors which bare the TMP3/4-ALK translocation

Inflammatory myofibroblastic tumor Anaplastic large cell lymphoma Renal cell carcinoma

Tumors which bare the CLTC-ALK rearrangement

Inflammatory myofibroblastic tumor ALK positive large B cell lymphoma Extramedullary plasmacytoma

Tumors which bare the RANBP2-ALK translocation

Inflammatory myofibroblastic tumor ALK positive large B cell lymphoma Myeloid leukemia

Tumors which bare the ETV6-NTRK3 fusion

Infantile fibrosarcoma Inflammatory myofibroblastic tumor Congenital mesoblastic nephroma, cellular type AML/ALL Secretory carcinoma (breast) Mammary analogue secretory carcinoma (salivary) Pigmented spindle cell nevus of Reed / Spitz nevus Rare papillary thyroid carcinomas Rare GISTs

Tumors which can bare the following translocations: MEAF6-PHF1 EPC1-PHF1 EP400-PHF1 PHF1-TFE3 ZC3H7B-BCOR

Endometrial stromal sarcoma Ossifying fibromyxoid tumor

Tumors which bare the ASPACR1-TFE3 translocation

Alveolar soft part sarcoma Renal cell carcinoma

Tumors which bare the MALAT1-GLI1 translocation

Gastroblastoma Plexiform fibromyxoma GLI1-altered epithelioid soft tissue tumor (malignant)

Tumors which bare the TGFBR3-MGEA5

Myxoinflammatory fibroblastic sarcoma Hemosiderotic lipomatous tumor Pleomorphic hyalinizing angiectatic tumor

How to remember the synovial sarcoma translocation

Synovial Sarcoma on chr18 :: Synovial Sarcoma on chrX SS18::SSX

Recurrent translocation in embryonal rhabdomyosarcoma

Just kidding! We still have no idea. The most common mulecular feature is polysomy 8, but we still don't really know what causes this sarcoma.

Sarcoma and mesenchymal tumors Flashcards

(91 cards)