1) Pathology plays a key role in brain tumor diagnosis by examining tissue samples and tumor markers. 2) Initial intraoperative consultations provide preliminary diagnoses to guide surgery, while formal pathology reports final diagnoses and grades tumors. 3) Molecular markers like IDH1 mutations, 1p/19q codeletion, and MGMT promoter methylation provide diagnostic and prognostic information and help guide treatment decisions.

1. Tests related to diagnosis: Pathology and biological markers
Dr. Michael Buckland
Hosted by Cure Brain Cancer Foundation

2. Tests
related
to
diagnosis:
Pathology
and
biological
markers
Neuropathology
|
RPA
Hospital
&
Brain
and
Mind
Research
Ins<tute
Michael
Buckland
Brain
&
Mind
Research
Ins<tute

3. Pathology
The
role
of
the
pathologist:
i. Provide
intraopera<ve
consulta<ons
as
needed.
ii. Provide
final
tumour
diagnosis
and
grade
based
on
resected
<ssue.
iii. Guide
appropriate
ancillary
tests
for
molecular
markers
iv. Communicate
with
surgeons,
oncologists,
radia<on
therapists

4. Intraopera<ve
consulta<ons
• Neurosurgeon
sends
a
small
piece
of
<ssue
fresh
to
pathology
to
get
an
idea
of
the
tumour
type
to
guide
the
opera<on:
– Is
this
lymphoma
or
glioma?
– Is
this
high
grade
glioma
or
metasta9c
cancer?
– Is
this
tumour
or
demyelina9on?

5. Intra-­‐opera<ve
smear
1
3
4
2

6. 1
3
4
2
Intra-­‐opera<ve
frozen
sec<on

7. • The
smear
and
frozen
sec<on
report
is
a
PRELIMINARY
report
only.
• The
formal
pathology
(takes
a
week
or
so)
is
the
defini<ve
pathology
report
• 10%
of
frozen
sec<on
diagnoses
are
changed
with
the
formal
report.
Intraopera<ve
consulta<ons

8. Formal
Pathology
• Based
almost
exclusively
on
MORPHOLOGY
(i.e.
what
the
tumour
looks
like
down
the
microscope)
• Formalin
fixa<on;
embedding
in
paraffin;
5
micron
thick
sec<ons;
stained
with
H&E

9. cell
&
tumour
types
• Tumours
are
named
aZer
their
resemblance
to
normal
brain
cells.
• Glial
cells
(suppor<ng
cells
of
the
brain)
– astrocytes
(astrocytomas
&
glioblastomas)
– oligodendrocytes
(oligidendrogliomas)
– ependymal
cells
(ependymomas)
• Neurons
(ganglion
cells)
– gangliocytoma
– ganglioglioma

11. Tumour
grading
• WHO
system
• Based
on
curability
&
clinical
survival
I
à
Discrete
II
III
à
Infiltra<ve
IV
Grading
is
dependent
on
the
tumour
type
anda
variety
of
morphological
features

12. Molecular
Markers
• Isocitrate
dehydrogenase
muta<ons
(astrocytomas,
oligodendrogliomas)
• 1p/19q
codele<on
(oligodendrogliomas)
• MGMT
promoter
methyla<on
(glioblastomas)

13. Isocitrate
dehydrogenase
muta<ons
• Isocitrate
dehydrogenase-­‐1,
-­‐2,
&
-­‐3
are
enzymes
involved
in
energy
genera<on
• Muta<ons
in
IDH1
are
very
common
in
grade
II
and
grade
III
astrocytomas
and
oligodendrogliomas.
• The
PRESENCE
of
IDH1
muta<on
helps
confirm
diagnosis
• The
ABSENCE
of
IDH1
muta<ons
in
these
tumours
suggests
they
may
behave
more
aggressively
than
normal
(BUT
data
is
s9ll
preliminary)

14. 1p/19q
loss
in
oligodendroglioma
• Tumour
cells
lose
the
short
arm
of
chromosome
1
and
the
long
arm
of
chromosome
19
• Occurs
in
70-­‐80%
oligodendrogliomas,
very
rare
in
other
tumour
types

15. prognos<c/predic<ve
value
of
1p/
19q
loss
• Slower
growth
• Befer
therapeu<c
response
• Increased
median
survival
dura<on
– 1p/19q
co-­‐dele<on:
• WHO
Grade
II:
12-­‐15
years
• WHO
Grade
III:
>7
years
– No
1p/19q
co-­‐dele<on
• WHO
Grade
II:
5-­‐8
years
• WHO
Grade
III:
2-­‐3
years

16. relevance?
• Oncologists
may
decide
to
hold
off
on
treatment
if
there
is
1p/19q
loss
present.
• Oncologists
may
decide
to
treat
earlier
if
there
is
no
1p/19q
codele<on

17. fluorescence
in
situ
hybridisa<on
(fish)
analysis
of
1p
and
19q

18.
1p
loss
19q
loss
1p36/1q25
probes
19p13/19q13
probes
1p
FISH
19q
FISH

19. MGMT
promoter
methyla<on
• MGMT
is
a
DNA
repair
enzyme
• It
repairs
DNA
damage
caused
by
chemotherapy
• MGMT
promoter
methyla<on
is
a
measurement
of
the
“switching
off”
of
MGMT
• Glioblastomas
with
MGMT
methyla<on
respond
befer
to
chemotherapy

20. how
we
measure

21. relevance
• MGMT
methyla<on
status
is
really
only
relevant
in
glioblastomas.
• It
may
guide
the
choice
of
radiotherapy
or
chemotherapy
in
the
elderly
with
glioblastoma

22. •
www.-­‐sswahs.-­‐nsw.-­‐gov.-­‐au/-­‐RPA/-­‐Neuropathology