Embryonal Tumors

Question 1

What are the 5 molecular groups of Medulloblastomas?

Answer 1

-WNT-activated (10%)
-SHH-activated (30%)
-TP53-WT (~20%)
-TP53-Mutant (~10%)
-Group 3 Non-WNT/Non-SHH (20%)
-Group 4 Non-WNT/Non-SHH (40%)

Question 2

What are the 4 histologic variants of Medulloblastomas?

Answer 2

-Desmoplastic/Nodular
-Extensive nodularity
-Large cell/Anaplastic
-Classic

Question 3

WNT-activated Medulloblastoma:
-Age
-Location
-Prognosis

Answer 3

-Childhood
-Midline cerebellum, Vermis/Fourth ventricle, Middle cerebellar peduncle
-Good prognosis

Question 4

SHH-activated TP53-WT Medulloblastoma:
-Age
-Location
-Prognosis

Answer 4

-Infancy to young adults
-Cerebellar hemispheres, midline
-Intermediate-risk (better with “extensively nodular” histology)

Question 5

SHH-activated TP53-Mutant Medulloblastoma:
-Age
-Location
-Prognosis

Answer 5

-Kids (4-17 y/o)
-Cerebellar hemisphere, midline
-Poor prognosis

Question 6

Group 3 - Non-WNT/Non-SHH Medulloblastoma:
-Age
-Location
-Prognosis

Answer 6

-Infancy/Childhood
-Midline or Lateral Cerebellum
-Poor prognosis

Question 7

Group 4 - Non-WNT/Non-SHH Medulloblastoma:
-Age
-Location
-Prognosis

Answer 7

-All Ages (3:1 males)
-Midline cerebellum, Vermis/Fourth ventricle
-Intermediate risk

Question 8

Group 4 - Non-WNT/Non-SHH Medulloblastoma:
-Histology

Answer 8

-Classic

*small blue cells with nuclear molding; may have Homer-Wright rosettes

Question 9

Group 3 - Non-WNT/Non-SHH Medulloblastoma:
-Histology

Answer 9

-Classic & Large cell/Anaplastic

*Features of Anaplasia: Increased nuclear size, pleomorphism, numerous mitoses with atypical forms, cell “wrapping”

Question 10

SHH-activated TP53-Mutant Medulloblastoma:
-Histology

Answer 10

-Large cell/Anaplastic
»
Desmoplastic/Nodular

Question 11

SHH-activated TP53-WT Medulloblastoma:
-Histology

Answer 11

-Desmoplastic/Nodular & Extensively Nodular

Question 12

WNT-activated
Medulloblastoma:
-Histology

Answer 12

-Classic

Question 13

Group 4 - Non-WNT/Non-SHH Medulloblastoma:
-Genetic alterations (3)

Answer 13

-MYCN amplification
-Isodicentric 17q
-KDM6A mutation

Question 14

Group 3 - Non-WNT/Non-SHH Medulloblastoma:
-Genetic alterations (3)

Answer 14

-MYC amplification
-PVT1-MYC fusion
-Isodicentric 17q

Question 15

SHH-activated TP53-Mutant Medulloblastoma:
-Genetic alterations (4)

Answer 15

-TP53 mutation
-MYCN mutation
-GLI2 mutation
-17p loss

Question 16

SHH-activated TP53-WT Medulloblastoma:
-Genetic alterations (4)

Answer 16

-PTCH1 mutation
-SUFU mutation
-SMO mutation
-TERT promoter mutations

Question 17

WNT-activated
Medulloblastoma:
-Genetic alterations (2)

Answer 17

-CTNNB1 mutation
-Monosomy 6

Question 18

Group 4 - Non-WNT/Non-SHH Medulloblastoma IHC profile:
-B-catenin
-GAB1
-FilaminA
-YAP1

Answer 18

-B-catenin: +; Cytoplasmic

-GAB1: NEG.

-FilaminA: NEG.

-YAP1: NEG.

Question 19

Group 3 - Non-WNT/Non-SHH Medulloblastoma IHC profile:
-B-catenin
-GAB1
-FilaminA
-YAP1

Answer 19

-B-catenin: +; Cytoplasmic

-GAB1: NEG.

-FilaminA: NEG.

-YAP1: NEG.

Question 20

SHH-activated TP53-Mutant Medulloblastoma IHC profile:
-B-catenin
-GAB1
-FilaminA
-YAP1

Answer 20

-B-catenin: +; Cytoplasmic

-GAB1: +; Cytoplasmic

-FilaminA: +; Cytoplasmic

-YAP1: +; Nuclear & Cytoplasmic

Question 21

SHH-activated TP53-WT Medulloblastoma IHC profile:
-B-catenin
-GAB1
-FilaminA
-YAP1

Answer 21

-B-catenin: +; Cytoplasmic

-GAB1: +; Cytoplasmic

-FilaminA: +; Cytoplasmic

-YAP1: +; Nuclear & Cytoplasmic

Question 22

WNT-activated
Medulloblastoma IHC profile:
-B-catenin
-GAB1
-FilaminA
-YAP1

Answer 22

-B-catenin: +; Nuclear & Cytoplasmic

-GAB1: NEG.

-FilaminA: +; Cytoplasmic

-YAP1: +; Nuclear & Cytoplasmic

Question 23

Embryonal Tumor with Multilayered Rosettes (ETMR), ______-altered.
-Defining molecular alteration

Answer 23

-C19MC (microRNA) Upregulation via amplifications and fusions

Question 24

Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC-altered:
-Age
-Location
-Prognosis

Answer 24

-0-4 y/o
-Cerebral hemispheres (70%); cerebellum & brainstem (30%)
-Poor prognosis

Question 25

Embryonal Tumor with Multilayered Rosettes (ETMR), C19MC-altered:
-Diagnostic marker

Answer 25

-LIN28A* (cytoplasmic reactivity)
-SMARCB1 (INI1): Diffuse positivity

*Not specific - also positive in AT/RT (Loss of INI1); gliomas (+/-)

Question 26

Atypical Teratoid/Rhabdoid Tumor (AT/RT):
-Age
-Location
-Grade

Answer 26

-Infants (< 3 y/o); ~3:2 Male
-Supratentorial > Intratentorial; may be multicentric
-WHO grade 4 - Aggressive

Question 27

Atypical Teratoid/Rhabdoid Tumor (AT/RT):
-Hallmark molecular alteration

Answer 27

Loss of SMARCB1 (INI1/SNF5)

*Rarely loss of SMARCA4 (BRG1)

Question 28

Atypical Teratoid/Rhabdoid Tumor (AT/RT):
-Diagnostic Marker
-Other IHC

Answer 28

-Loss of BAF47 reactivity (Marker for loss of INI1 protein expression)

-Variable expression of EMA, SMA, GFAP, Synaptophysin, Cytokeratins, Vimentin

Question 29

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Question 36

Question 37

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Question 40

Question 41

Synaptophysin

Question 42

Synaptophysin

Question 43

Question 44

Question 45

Question 46

Question 47

Question 48

Question 49

Question 50

Question 51

Question 52

Question 53

YAP1

Question 54

Question 55

B-Catenin

Question 56

Question 57

GAB1

Question 58

P53

Question 59

Reticulin

Question 60

Question 61

YAP1

Question 62

GAB1

Question 63

B-Catenin

Question 64

MYC (ish)

Question 65

Chr6

Question 66

Question 67

Question 68

INI1

Question 69

Question 70

Question 71

Question 72

Question 73

Question 74

Question 75

Question 76

Question 77

AE1/AE3

Question 78

EMA

Question 79

GFAP

Question 80

INI1

Question 81

Question 82

Question 83

Vimentin

Question 84

Neurofilament

Question 85

Synaptophysin

Question 86

SMA

Question 87

Answer 87

Embryonal Tumor with Multilayered Rosettes (ETMR)

Question 88

LIN28A

Question 89

Question 90

Question 91

Question 92

Question 93

Question 94

Question 95

Synaptophysin

Question 96

Question 97

Question 98

Question 99

Question 100