SLIDE SEMINAR CASES 5-8

Arie Perry, M.D. Director, Neuropathology

School of Medicine

CASE 5

• 4-year-old girl

• Headache, nausea, vomiting, and unsteady gait

• MRI shows a 7 x 6 cm heterogeneously enhancing right frontal tumor and obstructive hydrocephalus

FLAIR FLAIR + C

DWI ADC

INI-1

Ki-67

GFAP SYN

NFP Neu-N NFP Neu-N

OLIG2

LIN28A ETANTR control

School of Medicine

DIAGNOSIS: CNS PNET, WHO GRADE IV

Heidelberg Report

School of Medicine

CASE 6

• 9-year-old boy

• Headaches, nausea/vomiting, behavioral changes and difficulty speaking

• Head MRI: 3.6 cm peripherally enhancing, partially cystic mass centered in the right thalamus

Smear

FS

GFAP SOX2

SYN NFP

IDH1-R132H p53

ATRX BRAF V600E

H3.3 K27M Trimethyl H3.3

Control

School of Medicine

ADDITIONAL FINDINGS

• OLIG2 and Neu-N negative

• Monosomy 10 by FISH

• EGFR gene amplification by FISH

• MGMT non-methylated

School of Medicine

DIAGNOSIS: GLIOBLASTOMA, WHO GRADE IV

Sturm et al.,

Cancer Cell

2012;22:425-437

School of Medicine

CLINICAL FOLLOWUP

• Rx: STR, RT, TMZ, lapatanib

• Later Rx: vaccine trial, avastin

• CSF cytology positive 9 mo later

• Patient expired about 13 mo after dx

School of Medicine

CASE 7

• 9-year-old boy

• 2 month history of weight loss, change in mental status and blindness

• MRI: large enhancing tumor arising from the frontal skull base

EMA PR

SSTR2A

Ki-67=25%

School of Medicine

DIAGNOSIS: ANAPLASTIC MENINGIOMA, WHO GRADE III

HPC MIII

HPC

EMA CD34

USCAP Meeting 2014: Mod Pathol 27;Supp 2, 439A, 2014

Genetics

• Translocations and inversions of Chr 12q13

• NAB2-STAT6 fusion

Nat Genet. 2013;45(2):131-2.

Acta Neuropathol. 2013;125(5):651-8.

Acta Neuropathol. 2013;125(5):651-8.

STAT6

HPC Giant Cell SFT

ANA Meningioma ANA Meningioma

School of Medicine

CASE 8

• 9-year-old boy

• Headaches and vomiting

• MRI: pineal region mass with aqueductal compression and associated hydrocephalus

• CSF studies revealed an elevated beta HCG of 11 (normal <1.5 IU/L)

Smear

FS

GFAP SYN

INI-1

NFP

Ki-67=6%

School of Medicine

DIAGNOSIS: PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION, WHO GRADE III

Histologic subtype PCs PPTID

(low grade)

PPTID

(high grade)

PBs

Age group Adulthood Adulthood Childhood

Gross/radiologic appearence Rounded

Well-circumscribed

Pushing borders

Not yet clearly determined Irregular, lobulated

Ill-defined margins

Invasion

WHO grade I II III IV

Morphology Pineocytomatous rosettes

Density : moderate

Cells : medium-sized

Cytoplasm : clear or eosinophilic with

ill-defined limits

Nuclei : moderate size, round or indented

with inconspicuous nucleoli

Chromatin : thin or “ salt and pepper ”

Two architectures : diffuse or pseudolobulated

Transitional : Typical PC areas in continuity with PPTID component

Density : moderate to high

Cells : medium-sized to small

Cytoplasm : still visible

Nuclei : globally round with moderate anisocaryosis

Chromatin : “ salt and pepper ” with sometimes conspicuous nucleoli

Patternless architecture

Homer-Wright rosettes

Flexner-Wintersteiner rosettes, fleurettes (extremely rare)

Density : high

Cells : small

Cytoplasm : scant

Nuclei : carrot-shaped, round

Chromatin : hyperchromatic

Synaptophysin Strong, especially in pineocytomatous

rosettes

Cytoplasmic, weak to moderate Weak intensity, diffuse or focal

Mitoses 0

+++

6

++

6

+/-

6

++

Variable

+/- Neurofilament protein

Main treatments Surgery Optimal treatment not yet rated, but including surgery and at least one adjuvant

treatment

Surgery/radiotherapy/chemotherapy

Prognosis 8 Favorable

5-yr survival= 91%

Risk of local and delayed relapse

5-yr survival= 74%

Risk of metastatic dissemination

5-yr survival= 39%

Dismal

5-yr survival= 10%

Courtesy of Dr. Anne Jouvet