Keywords
stereotactic biopsy - diagnostic yield - accuracy
Introduction
Intracranial lesions often present neurosurgeons with diagnostic challenges when they
are found in areas with difficult surgical access or when they display features of
lesions that would require nonsurgical treatment.[1] Accurate histopathological diagnosis and molecular profiling are vital in determining
the course of treatment. This can be obtained through excision of the lesion or a
biopsy. Stereotactic brain biopsy, since its advent in the 19th century, has undergone
major modifications and innovations to improve its accuracy and clinical use.[2] Frameless and frame-based systems are often subjected to head-to-head comparisons.
While the frame-based stereotactic method has traditionally been considered the “gold
standard” method of biopsy, a recent large meta-analysis has proven that the frameless
system is comparable to its counterpart.[3]
An initial experience with the Cosman–Roberts–Wells (CRW) stereotactic frame was published
by Couldwell and Apuzzo in the 1990.[4] They cited comparable accuracy to the preexisting Brown–Roberts–Wells (BRW) system.
The CRW frame employs an arc-radius design that many find easy to use and is currently
used regularly in the neurosurgical centers in our country. The Albert-Wong (AW) stereotactic
frame, created by a Malaysian neurosurgeon in the year 2015, is based on linear algorithm.[5] A recent phantom-based accuracy study demonstrated that its accuracy is noninferior
to the traditional and well-established stereotactic frames.[5] The AW frame also boasts a simple and easy algorithm and stereotactic calculation
method. This frame is presently being used for intracranial lesion biopsies in hospitals
in the state of Sarawak, Malaysia. Methods used for stereotactic biopsies should not
be confined to a select few and ought to be modified and developed to suit and adapt
to the ever-expanding knowledge of stereotaxy. The frameless stereotactic biopsy method
has gained popularity and its widespread use is due to its versatility, efficiency,
and low complication rate.
We published a 5-year series of stereotactic biopsies in 2021, looking into factors
affecting diagnostic yield. The overall diagnostic yield acquired was only 76%, which
was below the average positive yield of other series.[6] Dhawan et al in their systematic review and meta-analysis of frame-based and frameless
stereotactic biopsies presented diagnostic yields ranging from 84 to 100%.[3] This prompted a review of methods and practices that we employed during our procedures.
Subsequently, we added new guidelines and made modifications, which we incorporated
into subsequent biopsies with the objective of improving our diagnostic yield.
Materials and Methods
This is a retrospective and prospective cross-sectional analytical study conducted
by the Department of Neurosurgery, Sarawak General Hospital. This study encompasses
a period of 8 years from the year 2014 to 2022. Sarawak General Hospital is a tertiary
hospital and serves as the largest hospital in the state of Sarawak. It involves all
patients undergoing stereotactic biopsies to diagnose intracranial lesions. The decision
for stereotactic biopsies was made by the neurosurgeon in charge on a case-to-case
basis.
Sample size was calculated using an 80% power and 90% confidence level using values
from previous studies.[5]
[6] The minimum number of patients required in each group was 30, which was achieved
in this study.
Biopsy Method
Stereotactic biopsy techniques used in our center consists of both frameless and frame-based
systems. These include the Portable Brainlab Vector Vision, Brain-suite Brainlab Curve,
CRW stereotactic frame, and the AW stereotactic frame. The choice of system used is
decided by the neurosurgeon based on his or her familiarity with the technique. These
biopsies were performed electively with a large proportion of frame-based biopsies
done under local anesthesia and monitored sedation in suitable patients. Frameless
biopsies were performed under general anesthesia. We used the Nashold biopsy needle,
Radionics (United States), which has a sampling window of 9.5 × 1.2 mm, located 2 mm
from the needle tip. The needle diameter is 1.8 mm, lumen is 1.5 mm, and the total
length is 29.8 cm. The tip of the needle is dome shaped with a window in the inner
cannula. This window can be aligned with the outer cannula window through rotation.
All biopsy specimens are sent for histopathological examination to the Pathology Department
of Sarawak General Hospital. A postoperative brain computed tomography (CT) is performed
immediately following the procedure to rule out a postbiopsy hemorrhage and to examine
the accuracy of the biopsy.
Changes in Practice
In an effort to improve our diagnostic yield and accuracy, we devised nine criteria/prerequisites
that would need to be fulfilled for each stereotactic biopsy procedure. They were
created and introduced after careful and meticulous examination of our previous biopsies
with negative yield and inaccuracy. A retrospective analysis of previous biopsy data
showed that a large proportion of negative yield (67 vs. 33%, >6 vs. < 6 weeks) occurred
in the cases where prebiopsy scans were greater than 6 weeks. Although this result
was not statistically significant (p < 0.05), we included this into our criteria as the proportion of negative yield was
considered high and the absence of statistical significance may be due to a limited
sample size. Preoperative steroids were given in 16 (32%) patients preoperatively,
with 6 of those patients having a negative biopsy yield (p < 0.05). With a large proportion of central nervous system (CNS) lymphoma in our
biopsy results, corticosteroids were seen as a major factor that may influence diagnostic
yield.
The new stereotactic biopsy criteria/prerequisites that were introduced in the year
2020 are the following:
All cases of stereotactic biopsies for intracranial lesions performed to acquire histopathological
diagnosis were included in this study. Cases done before the year 2014 and after 2022
were excluded. Our previous published study[6] was used as a comparison to evaluate the effects of the current changes in practice.
We compared the diagnostic yield and accuracy of 50 patients from 2014 to 2019 previously
reported by us with a new group of patients undergoing biopsy from 2020 to 2022. These
patients were grouped into two groups, with group 1 being cases done before the year
2020 prior to the introduction of new stereotactic biopsy criteria/prerequisites and
group 2 being cases done after the year 2020. The authors along with the operating
surgeon were responsible to ensure the adherence of each procedure to the criteria/prerequisites
for patients in group 2.
Data Collection and Analysis
Data were collected retrospectively for cases done before the year 2020 and prospectively
for cases after that year. Fifty patients who were included in the study published
from our center previously were also included in this present study for analysis.[6] These patients meet the inclusion criteria for our study and their inclusion adds
significant value to the present study. Patients' sociodemographic, clinical, and
radiological data were acquired from medical records and radiology database. Operative
details were collected from the operating theater database. The data were tabulated
in Microsoft Excel and analyzed using the SPSS software version 20.0 (SPSS Inc., Chicago,
IL, United States). Frequency distribution table, bar charts, means, and percentage
were used for descriptive data. Chi-squared, independent sample t-test, odds ratio, and 95% confidence interval were calculated. A p-value of less than 0.05 was considered statistically significant.
Outcomes
The primary outcome was measured via the yield of the histopathological specimen sent
for analysis. Positive yield includes but is not limited to a histopathological report
of a neoplasm, infection, inflammation, demyelination, etc. The secondary outcome
was measured via postoperative CT showing iatrogenically inserted air within the lesion.
Air present outside of the lesion was defined as an inaccurate biopsy radiologically.
Results
Of a total of 83 patients undergoing stereotactic biopsy, the mean age was 50.8 years,
with the majority (63%) of patients being of male ([Table 1]). A large proportion of lesions were located in deep sites (64%), with 53% being
less than 10 mL in volume ([Table 1]). The overall diagnostic yield of all biopsies from 2014 to 2022 was 84% ([Table 1]). There was a shift of preference toward frame-based methods after 2020, with 85%
of the 33 biopsies being frame based ([Table 2]).
Table 1
Sociodemographic, lesion, and biopsy characteristics (n = 83)
|
Variables
|
Frequency (%)
|
|
Gender
|
|
Male
|
52 (63)
|
|
Female
|
31 (37)
|
|
Age (mean)
|
50.8
|
|
Lesion location
|
|
Lobar
|
24 (29)
|
|
Cerebellum
|
4 (5)
|
|
Basal ganglia
|
16 (19)
|
|
Brainstem
|
5 (6)
|
|
Thalamus/hypothalamus
|
14 (17)
|
|
Pineal
|
3 (4)
|
|
Corpus callosum
|
14 (17)
|
|
Periventricular
|
3 (4)
|
|
Deep location
|
53 (64)
|
|
Lesion size
|
|
> 10 mL
|
39 (47)
|
|
< 10 mL
|
44 (53)
|
|
Biopsy method
|
|
Frameless
|
45 (54)
|
|
Frame
based
|
38 (46)
|
|
Anesthesia
|
|
General anesthesia (GA)
|
59 (71)
|
|
Local anesthesia (LA)
|
24 (29)
|
|
System used
|
|
Portable
Brainlab Vector
|
15 (18)
|
|
Brain-suite Brainlab Curve
|
30 (36)
|
|
Cosman–Roberts–Wells (CRW) frame
|
19 (23)
|
|
Albert-Wong (AW) frame
|
19 (23)
|
|
Complications
|
12 (14)
|
|
Hemorrhage
|
5
|
|
Brain edema
|
1
|
|
Seizures
|
–
|
|
Neurological deficit
|
9
|
|
Cerebrospinal fluid (CSF) leak
|
–
|
|
Death
|
–
|
|
Positive histopathological yield
|
70 (84)
|
|
Glioblastoma
|
6 (7)
|
|
Central nervous system (CNS) lymphoma
|
31 (37)
|
|
Glioma other than glioblastoma
|
18 (22)
|
|
Infection/abscess
|
9 (11)
|
|
Metastasis
|
3 (4)
|
|
Germinoma
|
2 (2)
|
|
Infarct/necrosis
|
1 (1)
|
|
Radiological accuracy
|
76 (92)
|
Table 2
Baseline comparison and analysis of diagnostic yield and accuracy between groups 1
and 2
|
Variables
|
Group 1 (n = 50)
Frequency (%)
|
Group 2 (n = 33)
Frequency (%)
|
p-Value
|
|
Gender
|
|
Male
|
31 (62)
|
21 (64)
|
0.88
|
|
Female
|
19 (38)
|
12 (36)
|
|
Age (mean)
|
48.3
|
54.5
|
0.14
|
|
Lesion location
|
|
Deep
|
29 (58)
|
24 (73)
|
0.24
|
|
Superficial
|
21 (42)
|
9 (27)
|
|
Lesion size
|
|
> 10 mL
|
20 (40)
|
19 (58)
|
0.07
|
|
< 10 mL
|
30 (60)
|
14 (42)
|
|
Biopsy method
|
|
Frameless
|
40 (80)
|
5 (15)
|
0.01[a]
|
|
Frame-based
|
10 (20)
|
28 (85)
|
|
Overall complications
|
6 (12)
|
5 (15)
|
0.74
|
|
Radiological accuracy
|
44 (88)
|
32 (97)
|
0.15
|
|
Positive histopathological yield
|
38 (76)
|
32 (97)
|
0.01[a]
|
Note: Group 1 includes cases done before the year 2020 prior to the introduction of
new stereotactic biopsy criteria/pre-requisites and group 2 includes cases done after
the year 2020.
a Statistically significant.
Fifty patients underwent stereotactic biopsies prior to implementation of the new
stereotactic biopsy criteria/prerequisites in 2020 with a positive histopathological
yield of 76% and a radiological accuracy of 88% ([Table 2]). Thirty-three biopsies were done postimplementation, with a positive histopathological
yield of 97% and a radiological accuracy of 97% ([Table 2]). This improvement was statistically significant (p < 0.05).
Subgroup analyses were performed to determine the effects of confounding factors on
the outcome between the two groups. [Table 3] demonstrates no significant difference in diagnostic yield between frameless and
frame-based biopsies for both groups and even when analyzed separately for groups
1 and 2. [Table 3] also demonstrates a significant difference between lesion size (<10 vs. >10 mL)
and diagnostic yield. However, when separately analyzed between the two groups, no
statistically significant difference was found.
Table 3
Frame-based versus frameless method, lesion size >10 versus <10 mL, and diagnostic
yield
|
Variable
|
Positive yield
Frequency (%)
|
Negative yield
Frequency (%)
|
p-Value
|
|
Overall
|
|
Frame based
|
35 (50)
|
3 (23)
|
0.07
|
|
Frameless
|
35 (50)
|
10 (77)
|
|
Group 1
|
|
Frame based
|
7 (18)
|
3 (25)
|
0.62
|
|
Frameless
|
31 (82)
|
9 (75)
|
|
Group 2
|
|
Frame based
|
28 (88)
|
0 (0)
|
0.15
|
|
Frameless
|
4 (12)
|
1 (100)
|
|
Lesion size
|
|
|
> 10 mL
|
37 (53)
|
2 (15)
|
0.01*
|
|
< 10 mL
|
33 (47)
|
11 (85)
|
|
Positive yield
|
|
|
|
Group 1
|
Group 2
|
|
> 10 mL
|
18 (47)
|
19 (59)
|
|
0.3
|
|
< 10 mL
|
20 (53)
|
13 (41)
|
Note: *Statistically significant.
Subgroup Analysis to Determine the Effects of Confounding Factors
Findings of the subgroup analysis to determine the effects of confounding factors
are shown in [Table 3].
Discussion
This 8-year analysis of stereotactic biopsies in our center clearly demonstrates a
significant improvement in positive diagnostic yield resultant from the introduction
of good practice criteria and prerequisites for these procedures. The improvement
was statistically significant (76 vs. 97%, p < 0.05). Following a review of stereotactic biopsies done in our center before the
year 2020, we identified numerous reasons and factors that we believe played a role
in the inaccuracy and negative histopathological yield.
Preoperative Scan Timing and Biopsy Planning
Preoperative scans closer to the time of biopsy would aid with the accuracy of the
planning of the target. Malignant tumors of the brain, in particular glioblastoma,
have a propensity for rapid growth, which would alter the selection of optimal biopsy
target; hence, a scan performed at a longer time interval from the day of biopsy might
not be representative of the actual tumor at that time.[7] Although being rather rudimentary in the planning of biopsies, the importance of
meticulous planning of target, entry point, and trajectory could not be stressed more
to achieve successful biopsies. The target is essentially chosen from areas of the
lesion with contrast enhancement as this results in better diagnostic yield.[8] The trajectory of the biopsy needle is carefully delineated in a computer software
that allows 3D viewing and a Probe's eye view. Studies have described the importance
of trajectory planning in deep brain stimulation and stereoelectroencephalography
(SEEG) where precision is of utmost importance.[9]
[10] Selecting a needle path that avoids the ventricles, sulcus, and important neurovascular
structures with the shortest distance to the target is imperative.
Frame and Coordinates
The frame-based biopsy has been considered by many to be the “gold standard” of accurate
biopsies.[8]
[11] However, the frame bulkiness and inherent technicalities pose a disadvantage to
this method. The performing surgeon needs to be extremely familiar with the choice
of frame or frameless system that is used. If a stereotactic frame is used, all the
parts and screws should be checked as a faulty part or a loose screw can cause geometrical
distortions, which would affect accuracy. The frames in our center, the CRW and AW
frames, have phantoms to check the target and trajectory coordinates. We also strongly
advocate the double checking of frame coordinates by two or more surgeons and the
review of the planned target and trajectory again with the frame fixed on the patient
to detect any gross inaccuracy, particularly on the side (right or left) of biopsy.
Corticosteroids and Methods to Minimize Brain Shift and Trajectory Deviation
Classical teaching advices against the use of corticosteroids in suspected cases of
primary CNS lymphoma. The reduction in diagnostic yield of these lesion with a pretreatment
of corticosteroids has been challenged by multiple studies.[12]
[13] Nonetheless, numerous studies have demonstrated the difficulty in reaching an objective
and consistent histopathological and immunohistochemical finding with patients having
administered steroids.[14]
[15] Primary CNS lymphoma accounted for the largest proportion of cases in our previous
biopsy analysis, and we have refrained from using corticosteroids for lesions planned
for stereotactic biopsy to reduce the possibility of a negative yield.[6] A sufficiently sized burr hole that is centered on the planned entry point is a
simple but often neglected detail that could cause the biopsy needle to skirt or be
obstructed by the outer or inner table of the skull. This would inadvertently result
in a deviation in the trajectory. The loss of CSF would prove costly in biopsies with
a small margin of error. The resultant shift in brain structures causes inaccuracies,
which have been reported in cases of deep brain stimulation.[16] These cortical and subcortical shifts also stem from the postural changes of intracranial
structures under the influence of gravity, pneumocephalus, and distortion of the cortical
and subcortical structures with the advancing biopsy needle. Thus, care must be taken
when durotomy is performed to minimize CSF egress, and needless to say excessive suctioning
of CSF is not recommended. The use of fibrin sealant has been advocated by some authors
in regard to this.[17]
Sampling Techniques and Examination of Acquired Sample
The method of acquiring a tissue sample during the biopsy is subject to a wide inter-user
variability depending on the surgeons' common practice and preference. The technique
of sampling consistently used at our center after the year 2020 is the “negative-pressure
and rotation” technique. The needle is advanced with a closed window into the brain
and upon reaching the target, the window is opened and the needle is rotated 360 degrees.
This achieves separation of the tissue through the cutting by the longer window edge.[18] Subsequently, the window is closed and the needle is removed. The addition of a
vacuum pressure through the aspiration of the syringe connected to the biopsy needle
has been shown to increase the quality, size, and mass of samples.[18]
[19] The biopsy sample should be examined for color and weight to be deemed satisfactory.
Clot-laden samples and buoyant specimens without significant mass are deemed suboptimal.
These criteria and prerequisites when applied to all stereotactic biopsies in unison
are bound to improve the accuracy and diagnostic yield as per the review above.
Conclusion
Simple and small details in routine surgical practice, although often underestimated
and overlooked, still remain important in improving the precision and efficiency of
surgical procedures as demonstrated in this study.
Limitations
The limitations of this study arise from its retrospective and prospective nature,
which limits the opportunity to adequately match and randomize patients into groups
and control. This is also contributed by the fact that the number of biopsy cases
is not large, which may have affected the statistical significance of the study. In
a high-volume center, a randomized or case control study would possibly improve the
statistical value of the study.
