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78
Clin
Pathol
1994;47:718-720
Brains
at
necropsy:
to
fix
or
not
to
fix?
A
Katelaris,
J
Kencian,
J
Duflou,
J
M
N
Hilton
Abstract
Aim-To
investigate
whether
routine
for-
malin
fixation
of
all
brains
coming
to
necropsy
increases
the
rate
of
detection
of
brain
abnormalities
relative
to
either
selective
formalin
fixation
of
brain
tissue
or
fresh
dissection
of
all
brain
tissue
at
the
time
of
post
mortem
examination.
Methods-A
retrospective
study
of
300
medicolegal
necropsies
was
performed.
One
hundred
cases
were
examined
by
doctors
with
little
or
no
formal
training
in
necropsy
pathology.
One
hundred
cases
were
examined
by
forensic
patholo-
gists,
who
used
their
discretion
as
to
whether
to
fix
the
brain
in
formalin.
A
further
100
cases
were
examined
by
neu-
ropathologists;
all
the
brains
had
already
been
fixed
at
the
time
of
necropsy.
Results-When
examined
by
doctors
with
little
or
no
formal
necropsy
pathology
training,
only
15%
of
brains
were
found
to
be
abnormal.
In
the
case
of
selective
fixation,
33%
were
found
to
be
abnormal.
When
there
was
obligatory
fixation
of
all
brains,
51%
of
all
brains
were
found
to
be
abnormal.
Conclusions-It
is
concluded
that
forma-
lin
fixation
of
the
whole
brain
at
the
time
of
necropsy,
followed
by
detailed
exami-
nation
of
the
brain
by
a
neuropathologist,
significantly
increases
the
detection
rate
of
brain
pathology
at
necropsy.
(7Clin
Pathol
1994;47:718-720)
NSW
Institute
of
Forensic
Medicine,
42-50
Parramatta
Road,
Glebe,
Sydney,
Australia
A
Katelaris
J
Kencian
J
Duflou
J
M
N
Hilton
Correspondence
to:
Professor
J
Hilton
Accepted
for
publication
9
February
1994
Neuropathologists
generally
believe
that
for-
malin
fixation
of
the
undissected
brain
removed
from
the
body
at
the
time
of
necropsy
is
preferable
to
dissection
of
the
fresh,
unfixed
brain
during
necropsy.'
2
Although
this
is
accepted
belief
we
have
been
unable
to
find
any
previous
publications
in
support
of
this
practice.
Removal
of
tissue,
including
the
brain,
from
the
body
at
necropsy
is
considered
by
some
to
be
a
contentious
issue,
because
it
contravenes
the
social
mores
of
many
cul-
tures,3
a
factor
made
much
of
by
the
popular
press.4
Formalin
fixation
of
the
brain
generally
takes
at
least
three
weeks
to
permit
optimal
examination
of
the
tissue.
This
results
in
a
substantial
delay
in
the
finalisation
of
a
necropsy
report.
Adequate
examination
of
brain
tissue
is
also
costly
and
time
consuming.
Furthermore,
there
is
a
worldwide
shortage
of
trained
neuropathologists.
Methods
A
retrospective
study
of
the
necropsy
reports
of
300
cases
was
conducted.
All
necropsies
were
conducted
as
part
of
an
investigation
required
by
the
New
South
Wales
(NSW)
Coroners'
Act.
This
Act,
when
read
in
con-
junction
with
the
Registration
of
Births,
Deaths
and
Marriages
Act,
requires
the
coro-
ner
to
investigate
sudden
unexpected
death,
deaths
occurring
under
suspicious
circum-
stances,
from
overt
or
covert
violence,
and
deaths
in
custody,
etc.
Similar
legislation
exists
in
all
states
and
territories
of
Australia.
In
the
Sydney
metropolitan
area
and
in
the
Hunter
region
of
New
South
Wales
the
inquiry
into
all
"coronial"
deaths
includes
a
comprehensive
postmortem
examination
by
specialist
forensic
pathologists
or
trainee
pathologists
under
their
supervision.
Outside
these
areas,
medicolegal
necropsies
are
con-
ducted
by
non-forensic
pathologists,
or
more
commonly,
by
non-specialist
doctors
known
as
government
medical
officers
(GMOs).
The
GMOs
may,
but
are
currently
not
required,
to
refer
material
to
the
New
South
Wales
Institute
of
Forensic
Medicine
for
further
examination,
usually
of
a
histological
nature.
The
material
to
which
this
study
relates
is
divided
into
three
groups:
Group
A-One
hundred
examinations
con-
ducted
in
rural
areas
of
New
South
Wales
by
GMOs
whose
usual
practice
is
to
dissect
brain
tissue
in
the
fresh
state
at
the
time
of
their
ini-
tial
examination.
The
necropsy
reports
and
histological
material
(which
did
not
necessarily
include
central
nervous
system
samples)
were
available
to
us.
Group
B-This
group
of
100
consecutive
cases
consisted
of
cases
coming
to
necropsy
at
the
New
South
Wales
Institute
of
Forensic
Medicine
in
1988
by
forensic
pathologists
or
pathology
trainees.
At
the
Institute
at
that
time
brains
were
dissected
fresh,
unless
an
opinion
was
to
be
sought
from
a
neuropathol-
ogist.
This
further
opinion
was
usually
sought
in
cases
of
complex
trauma
or
known
other
intracranial
pathology.
Group
C-The
third
group
of
100
consecutive
cases
consisted
of
cases
coming
to
necropsy
at
the
New
South
Wales
Institute
of
Forensic
Medicine
in
1992
by
forensic
pathologists
or
pathology
trainees.
All
these
brains
had
been
formaliin
fixed
and
were
then
examined
by
neuropathologists
or
forensic
pathologists
with
an
interest
in
neuropathology.
From
early
1991,
all
brains
from
bodies
examined
at
the
Institute
were
formalin
fixed
and
exam-
ined
in
this
way.
718
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Brains
at
necropsy:
to
fix
or
not
to
fix?
Decomposed
cases,
in
which
formalin
fixa-
tion
of
the
whole
brain
was
not
indicated,
were
not
included.
The
findings
were
grouped
into
categories
of
normal,
acute
trauma
to
the
brain,
and
other
neuropathology.
The
"other
neuro-
pathology"
group
included,
among
others,
cases
of
prolonged
survival
after
head
injury,
brain
tumours,
degenerative
brain
disease
and
cerebrovascular
disease
resulting
in
neuro-
logical
deficit.
Cases
of
non-complicated
atherosclerotic
cerebrovascular
disease
were
classified
as
normal
for
the
purposes
of
this
study.
The
null
hypothesis
that
there
would
be
no
difference
between
the
three
groups
in
their
assignment
of
the
various
diagnostic
cate-
gories
was
analysed
using
the
x2
test.
Results
Three
hundred
coronial
necropsy
reports
were
reviewed,
100
in
each
of
the
three
groups.
Table
1
shows
the
distribution
of
cases
by
manner
of
death
in
the
three
groups-there
were
no
significant
differences
between
the
groups.
The
brain
had
been
examined
in
all
cases.
Table
2
presents
the
frequency
of
neuropathological
findings
in
the
three
groups.
In
group
A
two
brains
had
been
fixed
whole
and
subsequently
examined
by
a
neuropathol-
ogist.
One
showed
a
large
superficial
cerebral
abscess
with
purulent
meningitis,
the
other
multiple
old
traumatic
lesions.
The
macro-
scopic
necropsy
report
described
pathological
lesions
in
a
further
13
cases:
there
were
eight
gunshot
wounds
to
the
head,
four
cases
of
severe
motor
vehicle
trauma
and
one
case
of
old
cerebral
infarction.
Table
1
Manner
of
death
Suicdel
Road
Medical
drug
traffic
Other
illness
overdose
trauma
trauma
Homicide
Undetermined
Group
A:
Necropsy
by
non-pathologist.
61
22
5
10
0
2
Tissue
referred
if
considered
necessary.
Group
B:
Necropsy
performed
by
forensic
64
9 10
17
0
0
pathologist.
Selected
brains
fixed
and
examined
by
neuropathologist.
Group
C:
Necropsy
performed
by
59
18
6
15
1
1
forensic
pathologist.
All
brains
formalin
fixed
and
examined
by
neuropathologist.
Table
2
Brain
dissection
findings
Group
A
Group
B
Unfixed
Ftxed
Total
Unfixed
Fixed
Total
Group
C
Normal
85 0
85
52
15
67
49
Acute
trauma
12
0
12
10 10
20
16
Other
neuropathology
1
2
3
8
5
13
35
Total
98
2
100
70
30
100 100
Group
A:
necropsy
performed
by
non-pathologist.
Tissue
referred
if
considered
necessary.
Group
B:
necropsy
performed
by
forensic
pathologist.
Selected
brains
fixed
and
examined
by
neuropathologist.
Group
C:
necropsy
performed
by
forensic
pathologist.
All
brains
fixed
in
formalin
and
examined
by
neuropathologist.
In
group
B
30%
of
brains
were
fixed
before
being
examined
by
a
neuropathologist.
Of
these,
50%
had
major
pathology.
In
contrast,
only
26%
of
the
brains
examined
in
the
unfixed
state
showed
extensive
pathological
lesions.
In
group
C
where
all
brains
had
been
fixed
before
examination,
51
%
showed
extensive
pathology.
This
was
a
higher
rate
of
detection
of
pathology
than
if
the
brain
had
been
exam-
ined
either
by
a
GMO
or
using
the
protocol
for
group
B.
When
comparing
the
various
groups,
the
difference
was
highly
significant
(X2
=
43-201;
df
=
4;
p
<
0-001).
This
is
mainly
due
to
the
difference
in
group
A
and
group
C
in
their
categorisation
of
"other
neuropathology".
There
was
no
significant
difference
in
the
detection
of
acute
trauma
pathology
between
the
various
groups.
The
data
were
farther
examined
using
2
x
2
x2
analyses,
comparing
differences
in
assign-
ment
to
diagnostic
categories
in
the
various
groups.
There
were
significant
differences
in
the
diagnoses
between
groups
A
and
B
(X2
=
10-38;
df=
2;
p
<
0006),
groups
A
and
C
(x2
=
37-19;
df
=
2;
p
<
0-0001),
and
groups
B
and
C
(X2
=
13-32;
df
=
2;
p
<
0-001).
Discussion
Fixation
of
whole
brains
removed
at
necropsy
may
be
an
emotive
issue.
Reliable
current
technology
entails
a
delay
in
completion
of
the
examination
of
at
least
three
weeks.
We
have
had
little
success
with
more
rapid
fixation
techniques,
including
microwave
fixation
of
the
brain.
Next
of
kin
may
not
want
to
bury
or
cremate
an
incomplete
body,4
although
ratio-
nal
explanation
of
the
nature
of
a
postmortem
examination
can
allay
these
concerns.
Routine
fixation
and
thorough
examination
of
all
such
brains
adds
considerably
to
the
cost
of
necropsy,
and
can
cause
major
difficulties
with
storage
and
later
disposal
of
the
tissues.
Suitably
qualified
neuropathologists
need
to
be
available,
at
least
on
a
part-time
basis.
They
are
a
scarce
resource
and add
further
to
the
real
but
often
hidden
cost
of
a
meaningful
postmortem
examination.
The
major
advantages
associated
with
this
method
of
examination
include
the
ability
to
perform
a
more
precise
and
useful
topo-
graphic
study
of
the
brain,
and
detection
of
small
but
important
lesions.2
Appropriate
blocks
for
histological
examination
can
be
more
readily
selected,
without
which
the
definitive
diagnosis
of
such
conditions
as
multiple
sclerosis,
Huntington's
chorea,
the
differential
diagnosis
of
the
later
onset
dementias,
diffuse
axonal
injury,5
etc,
may
not
be
made.
The
purpose
of
a
postmortem
examination
is
to
describe
and
delineate
pathological
processes
in
the
human
body.
The
medico-
legal
necropsy
is
also
directed
to
establishing
the
cause
of
death
for
the
coroner.
In
this
par-
ticular
study
detailed
examination
of
the
brain
did
not
materially
influence
the
establishment
of
the
cause
of
death
beyond
the
examination
719
group.bmj.com on July 16, 2011 - Published by jcp.bmj.comDownloaded from
Katelaris,
Kencian,
Duflou,
Hilton
of
other
organ
systems.
However,
pathology
in
addition
to
the
crude
cause
of
death
was
described
in
28%
of
the
cases
where
the
brain
was
adequately
examined
after
fixation.
So
although
proper
examination
of
the
brain
is
time
consuming
and
more
expensive,
neglect-
ing
so
to
do
would
be
a
dereliction
of
duty
for
what
is
in
essence
the
pathologist's
patient.
Our
study
shows
that
formalin
fixation
of
the
whole
brain
before
examination
results
in
a
significantly
increased
detection
rate
of
ante-
mortem
pathology.
Examination
of
unfixed
material
by
a
doctor
who
has
not
had
formal
postgraduate
training
in
pathology
results
in
a
low
detection
rate
of
both
traumatic
and
non-
traumatic
central
nervous
system
pathology.
GMOs
detected
no
small
or
diffuse
traumatic
lesions,
but
they
did
detect
a
problem
in
three
cases,
subsequently
confirmed
by
a
neuro-
pathologist.
More
subtle
non-traumatic
pathology
was
not
described
by
GMOs.
Fixation
of
preselected
brains
results
in
a
higher
detection
rate
of
important
pathology
as
illustrated
in
group
B.
By
comparing
the
results
of
groups
A
and
B
with
those
of
group
C,
we
have
shown
the
advantages
of
formalin
fixation
of
brains
before
examination
and
how
the
optimal
result
is
obtained
when
such
material
is
examined
by
a
neuropathologist.
We
conclude
that
the
advantages
of
exami-
nation
of
the
brain
after
fixation
outweigh
the
disadvantages
of
delaying
the
finalisation
of
the
necropsy
report.
At
necropsy
all
brains
should
be
fixed
before
detailed
examination
if
the
maximum
accurate
diagnostic
information
is
to
be
obtained.
1
Esiri
MM,
Oppenheimer
DR.
Introduction:
General
methodology
and
pathological
cellular
reaction.
In:
Diagnostic
neuropathology.
Oxford:
Blackwell
Scientific
Publications,
1989:2.
2
Okazaki
H.
Introduction.
In:
Fundamentals
of
neuropathol-
ogy.
New
York:
Igaku-Shoin,
1983:2.
3
Hill
RB,
Anderson
RE.
Decline
of
the
autopsy:
reasons
in
society.
In:
The
autopsy-Medical
practice
and
public
policy.
Boston:
Butterworths,
1988:165.
4
Ongaro
D.
The
last
rights:
Mum
in
rage
over
son's
brain
autopsy.
The
Daily
Telegraph
Mirror.
Sydney,
21
April
1992:28.
5
Simpson
RH,
Berson
SD.
The
postmortem
diagnosis
of
diffuse
cerebral
injuries,
with
special
reference
to
the
importance
of
brain
fixation.
SAfrMedJ1
1987;71:10-4.
720
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doi: 10.1136/jcp.47.8.718
1994 47: 718-720J Clin Pathol
A Katelaris, J Kencian, J Duflou, et al.
Brains at necropsy: to fix or not to fix?
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