Key words
aneurysmal bone cyst - selective arterial embolization - sacrum - bone tumor
Introduction
The aneurysmal bone cyst (ABC) is a benign bone lesion comprising approx. 1 % of all
primary osseous lesions. The typical patient’s age is below 20 years [1]. Although ABC was initially described by Jaffe and Liechtenstein in 1942, to-date
little is known about its origin. The ABC consists of cyst-like chambers made up of
fibrous tissue filled with free-flowing blood [1]
[2]. The typical visual appearance in imaging is usually characterized by a balloon-like
thinned cortex as well as multiple septa [3]. Detection of mirroring and contrast agent absorption by the cystic membranes in
magnetic resonance imaging (MRI) should be assessed as almost pathognomonic [4]. Generally ABCs are localized in the metaphyses and diaphyses of the long bones;
they infrequently also occur on the spine or in the pelvic region [5]. In extraordinary cases, an ABC can be localized on the sacrum. Mirra describes
only three cases in his study cohort of 492 cases [1].
If ABC is suspected, the diagnosis should always be confirmed by biopsy. CT-guided
procedures are suitable for this [6]
[7]. Especially in the case of solid tumor components, malignant bone lesions such as
low-malignant central osteosarcoma or telangiectatic osteosarcoma should be ruled
out. Further, the ABC should be distinguished from a so-called secondary aneurysmal
bone cyst which can occur as a secondary phenomenon of other bone lesions such as
giant cell tumor.
Clinical symptoms of ABC are generally non-specific; however, stress-related pain
is frequently reported. If the ABC is located on the spine or in the sacral region,
space-occupying ballooning of the cortex may also cause compression of the spinal
cord or nerve roots, usually manifested by neurological deficits.
Treatment of an aneurysmal bone cyst is the subject of ongoing discussions. If the
ABC is located in the area of the long bones, treatment usually consists of curettage
of the cyst, followed by plombage with bone cement or filling with bone or bone replacement
material [8]
[9]. Other approaches employ local cryotherapy or application of sclerosing agents such
as polidocanol [10]
[11]
[12]
[13]. Surgical intervention in the spinal or sacral region is not without risk, as it
can result in damage to the myelon or nerve roots with accompanying permanent neurological
deficits. Furthermore, there are individual case reports of drug treatment using denosumab,
but this is likewise risky and has not been approved for treating ABC [14].
Previously, transarterial embolization of bone lesions was generally performed as
a preoperative measure to reduce hemorrhaging [15]
[16]
[17]
[18]
[19]. However, a few recent publications have reported using embolization as a primary
treatment of bone lesions at unfavorable anatomical locations [20]
[21]
[22]. The aim of this retrospective study was to evaluate the effectiveness of using
transarterial embolization of ABCs of the sacrum as the sole treatment mechanism.
Materials and Methods
This retrospective study included all patients in our tumor database who were diagnosed
with a primary aneurysmal bone cyst of the sacrum via biopsy and who then were treated
using transarterial embolization. In total, between 2007 and 2011 six patients (two
girls, four boys), between 8 – 18 years of age were treated (average age 13.7 years,
[Table 1]). The period of time between initial MRI imaging and embolization was a maximum
of eight weeks. Clinical data were taken from the patients files, including information
from the clinical examination and case history collected in the course of aftercare.
This also included asking about pain analogously to the numeric rating scale (NRS),
in which the patient has to rate pain according to a scale ranging from 0 (no pain)
to 10 (maximum imaginable pain). Data were collected during every patient contact.
Table 1
Patient data, symptoms at time of first presentation including intensity of pain and
duration of symptoms.
|
patient
|
age
(years)
|
gender
|
symptoms
|
duration of symptoms (months)
|
|
1
|
15
|
female
|
lower back pain, pain in left thigh (NRS 5)
|
12
|
|
2
|
8
|
male
|
lower back pain (NRS 6), 4/5 paresis of right S1, trendelenburg gait, paresthesia
right heel
|
1
|
|
3
|
14
|
female
|
lower back pain, pain in left gluteal (NRS 6)
|
3
|
|
4
|
18
|
male
|
no pain (NRS 0), incidental finding (PET CT)
|
0
|
|
5
|
11
|
male
|
pain right gluteal (NRS 5)
|
11
|
|
6
|
16
|
male
|
pain in right sacral bone (NRS 9), left scrotal paresthesia, bladder dysfunction
|
6
|
NRS = numeric rating-scale.
In the first year after embolization, MRI examinations were performed every three
months as follow-up and to rule out interventional complications (e. g. osteonecrosis);
after that, the interval was extended to six months. After two years had passed, annual
MRI follow-up examinations were recommended. The MR images were produced in various
institutes; evaluation, however, was performed in one institute by two independent
assessors. Local lesion monitoring (no further lesion growth/regression) as well as
pain reduction/elimination were considered to be therapeutic success. In addition,
changes to the interior structure of the cysts were documented. Enlargement of the
ABC after initial embolization as well as persistent/progressive clinical symptoms
were considered indications for repeated transarterial embolization.
Treatment
The goal of interventional therapy is the primary particle embolization of the tumor
bed to completely devascularize the ABC. In all cases a diagnostic overview and selective
angiography were performed first to evaluate the arterial tumor flow ([Fig. 1a], [2a]). A 4 or 5 French introducer sheath [Radifocus Introducer II, Terumo Europe N.V.,
Belgium] was inserted in all patients using a retrograde arterial access point via
the femoral artery as an introitus. Selective vascular exploration used either a UF,
cobra or vertebral catheter [SUPER TORQUE Angiographic Catheter, Cordis/Johnson &
Johnson Europe, Ireland; Tempo 5 Angiographic Catheter, Cordis/Johnson & Johnson Europe,
Ireland]; the DSA series were acquired using mechanical contrast agent application.
Fig. 1 a Pre-therapeutical DSA picture showing the vascular supply of a huge aneurysmal bone
cyst of the sacrum. Main vessels derive from the internal iliac artery. In contrast
to the surrounding area a hypervascularisation can be seen. b DSA-Series after embolisation with PVA particles showing an almost complete devascularisation
of the ABC.
Fig. 2 a DSA-picture showing a hypervascularised ABC of the sacrum with several feeding vessels
deriving from the internal iliac artery. b Angiogram after selective arterial embolisation. With a combination of coils and
350 – 500 μm sized PVA-particles an embolisation of the main supplying vessels lead
to an 80 % devascularisation of the ABC.
A hypervascularized tumor bed was diagnosed in 4 patients during the initial angiography.
In addition, 2 patients demonstrated outflow via collaterals which had to be closed
using protective coil embolization by means of thrombogenic microcoils to avoid undesirable
particle outflow prior to tumor embolization itself [Tornardo Embolization Coil, Cook
Medical Europe, Ireland]. Supraselective exploration of the branches supplying the
ABC used a micro-catheter and micro-wire [Progreat, Terumo Europe N.V., Belgium; Fathom
Steerable Guidewire, Boston-Scientific Europe, France]; embolization of the tumor
bed utilized PVA particles [Contour, 355 – 500 μm, Boston-Scientific Europe, France;
Embocept, 400 μm, Pharmacept; Embozene Microspheres, 400 μm, CeloNova Biosciences,
Texas].
Two of the patients did not demonstrate a hypervascularized tumor bed, and the vascular
branches supplying the cysts were closed via coil embolization [Tornardo Embolization
Coil, Cook Medical Europe, Ireland].
After embolization, a final DSA series was obtained in order to determine the level
of devascularization ([Fig. 1b], [2b]). If the tumor grew or if pain persisted, an angiography and subsequent arterial
embolization were repeated.
Results
Initial radiological and clinical findings
The MR images demonstrated an average pre-interventional tumor volume of 145.5 cm3 (25.34 to 365.20 cm3). The midline was exceeded in four cases ([Table 2]).
Table 2
Location and initial dimension of sacral aneurysmal bone cyst, measured in cm3. Additionally shown is the dimension at last MRI follow-up. Radiological and clinical
follow-up in months.
|
patient
|
location
(massa lateralis)
|
initial cyst volume in cm3
|
cyst volume at last follow-up in cm3
|
follow-up
MRI
|
clinical follow-up
|
|
1
|
left, S2 – S3
|
365.20
|
65.86
|
32 months
|
32 months
|
|
2
|
right, S1 – S2
|
185.76
|
184.70
|
36 months
|
39 months
|
|
3
|
left, S1 – S2
|
181.83
|
158.69
|
28 months
|
35 months
|
|
4
|
left, S1 – S2
|
25.34
|
8.75
|
35 months
|
43 months
|
|
5
|
right, S2 – S5
|
57.46
|
11.31
|
54 months
|
56 months
|
|
6
|
left, S2 – S4
|
57.41
|
54.54
|
10 months
|
14 months
|
Prior to treatment, lower back pain was reported as the most frequent symptom.
Two patients had recurrent sciatica. The average pre-interventional pain intensity
came up to 6 of 10 (NRS, numeric rating scale, range 4 – 9). Pre-therapeutic neurological
deficits were documented for two patients. One patient presented with 4/5 paresis
of S1; in another patient, scrotal sensitivity deficit combined with bladder function
impairment was determined. Symptom duration ranged from 1 to 12 months ([Table 1]). In one patient, ABC was detected using PET-CT as incidental findings in the course
of follow-up of Ewing’s sarcoma of the tenth rib and concurrently occurring lung metastasis
that had been diagnosed four years previously; six months prior to this, the PET-CT
was unremarkable.
Results of transarterial embolization
The transarterial embolization resulted in complete devascularization (100 %) in three
patients; 80 % devascularization was achieved for the other patients. The degree of
devascularization was estimated using a subsequent DSA series. Treatment-related complications
were not observed ([Table 3]).
Table 3
Overview of success, subsequent treatment and treatment-related complications. In
addition, symptoms remaining after TAE are shown.
|
patient
|
degree of estimated devascularization
|
subsequent treatment
|
complications after TAE
|
symptoms after TAE
|
|
1
|
80 %
|
none
|
none
|
none, NRS 0
|
|
2
|
100 %
|
none
|
none
|
none, NRS 0
|
|
3
|
80 %
|
none
|
none
|
none, NRS 0
|
|
4
|
1. 100 %, 2. 100 %
|
2. TAE
|
none
|
none, NRS 0
|
|
5
|
100 %
|
none
|
none
|
none, NRS 0
|
|
6
|
1. 80 %, 2. 100 %, 3. 100 %
|
2. TAE decompression 3. TAE
|
none
|
paresthesia, intermittent NRS 1
|
TAE = Transarterial Embolization, NRS = Numeric Rating Scale.
Radiological post-treatment examination
The average post-treatment examination time frame using MRI was 32.2 months (10 – 54
months, [Table 2]). The objective of local tumor control was achieved with all patients. In four of
the six patients, growth inhibition of the ABC was observed after the first embolization;
two patients required a second treatment, and one required a third. Over time, regression
of the ABC was observed in three of six patients; in these cases the cystic components
developed into solid tissue ([Fig. 3], [4], [5]). The average tumor volume was reduced over time from 145.5 cm3 to 80.64 cm3 ([Table 2]).
Fig. 3 Axial MRI-scan (T1 TSE with contrast medium) of a 15 year-old girl revealing a huge
ABC of the sacrum. The initial, pre-therapeutical expansion measures 8.0 × 5.5 × 8.3 cm
with extension to the midline. In addition a huge ventral component can be seen.
Fig. 4 Axial MRI scan (T1 TSE FS with contrast medium) 18 months after embolisation. A shrinking
of the ABC to 3.0 × 5.4 × 5.0 cm can be detected. Further a reduction of cystic areas
and fluid levels can be detected.
Fig. 5 Axial MRI scan (T1 TSE FS with contrast medium) 32 months after embolisation. Minimal
further reduction of tumor size (2.8 × 4.8 × 4.9 cm) and ongoing transformation of
cystic areas into fibrous components.
Clinical post-treatment examination
The average post-treatment clinical examination time frame was 36.5 months (14 – 56
months, [Table 2]). Four of five symptomatic patients (incidental finding of ABC for Patient no. 4)
reported freedom from pain (NRS 0). One patient with a baseline 4/5 paresis of S1
demonstrated complete regression. After seven months, a second embolization was performed
on the patient with the coincidentally-discovered ABC, since MR imaging exhibited
additional size progression; consequently further growth was inhibited, and finally
an onset of consolidation was observed. Initially the sixth patient reported pain
intensity of nine on the NRS. The initial arterial embolization did not result in
lasting pain reduction; therefore one month later a second angiography and embolization
were performed. Complete devascularization was achieved after the second treatment.
Due to a sudden exacerbation of sciatica without an identifiable trigger, persistence
of scrotal paresthesia and previously reported bladder dysfunction, surgical decompression
and neurolysis were performed two months after the initial embolization. The sciatica
and bladder dysfunction immediately regressed but the lack of sensitivity in the scrotal
region persisted. When symptoms returned, only small-diameter blood vessels were detected
and embolized after a third angiography. After eight months the MRI demonstrated that
the size remained constant; pain was reported as only 1 (NRS). The patient could return
to work as a craftsman without restrictions.
Analysis
The goal of treating patients with aneurysmal bone cysts is local tumor control, freedom
from pain and restoration of normal anatomy [11]. In the extremities region, surgical treatment is the standard procedure. Generally,
curettage is performed; as a local adjuvant treatment, an application of phenol and/or
cryotherapy is employed [11]
[12]. Reconstruction of the bony defect uses bone (autogenous or allogenic), bone substitutes
or bone cement [9]
[11]
[23]. Another minimally-invasive therapeutic method is percutaneous injection of sclerosing
agents such as polidocanol [10]. Treatment of ABCs in the sacral region must be more sophisticated, and frequently
requires an interdisciplinary approach. Due to their location, ABCs are frequently
diagnosed only after they have expanded to the point where they create irritation
or compression of nerve roots or myelon. Pathological fractures of the sacrum causing
stress-related pain were not evident in our series of patients [24]. Complete curettage in the sacrum is generally not possible due to the proximity
of blood vessels and nerve roots; however there are reports of complication-prone
surgical interventions at this location. For example, Pogoda et al. report on an intralesional
resection of a large sacral ABC with an extensive ventral soft tissue component. During
the operation, the right-lateral components of sacral vertebrae 1 to 3 were removed.
To provide dorsal stability, instrumentation from lumbar vertebra 4 deep into the
sacrum was performed [25]. Brastianos and colleagues report of a series with 10 patients with an ABC of the
sacrum. Broad resection of the tumor was performed on patients with an ABC on the
caudal sacrum broad; on the other hand, curettage was performed in the cranial region
with protection of the nerve root. Four patients developed local recurrence (on average
17 months postoperatively); in two patients curettage also caused permanent vesicorectal
dysfunction [26]. Based on these reports, it should be questioned whether these risky and complication-laden
treatment procedures of a benign tumor are justified. Our data show that transarterial
embolization used for local lesion control (no further growth or regression) generally
results in complete symptom relief. Furthermore, no treatment-related complications
have been observed. Recent publications on minimally-invasive techniques (e. g. injection
of fibrosing agents or CT-guided injection of demineralized bone and bone marrow)
demonstrate that extensive operations can be avoided [2]
[16]
[27]
[28]
[29].
Likewise, percutaneous injection of polidocanol for sclerotherapy of the cyst is an
effective procedure; however, in the case of larger cysts, multiple applications using
anesthesia are required [13]. Sequential injection therapy in the sacral region can be usefully employed, especially
if angiography rules out a hypervascularized tumor bed, and embolization does not
appear to be medically sensible. An additional sclerosing agent is NBCA (N-2-butyl
cyanoacrylate). NBCA is successfully used for selective arterial embolization; there
are numerous studies of endovascular application in the treatment of ABC [20]
[21]. To-date there have been no large-scale studies of the percutaneous use of NBCA
in the treatment of ABC.
So far there are hardly any reports regarding transarterial embolization as a sole
method of treatment [28]
[29]. Generally embolization is used preoperatively to reduce bleeding [16]
[19]
[29].
Our series demonstrates that local tumor control can be achieved using transarterial
embolization as the sole treatment method. During a follow-up period averaging more
than two years there was no size progression; in the case of three patients a noticeable
regression was observed as well as partially solid remodeling of the cyst ([Fig. 3], [4], [5]). Even though long-term results are still pending, stopping cyst growth and remodeling
of cystic areas into solid components are indicative of long-lasting beneficial effects.
In this regard, only a small number of transarterial embolizations have been necessary.
Although in our cases, compared to other series, remineralization of the bone was
not observed, five of six patients are symptom-free, their neurological deficits indicated
regression [28]
[29]. The sixth patient reported that pain had subsided to the point where he could return
to work. All patients could engage in full weight-bearing sporting activities without
limitation. This suggests that with respect to aneurysmal bone cysts in the sacrum
compared to those in long bones of the extremities, restoration of the physiological
bone structure appears to be of secondary importance. In our opinion, based on the
above-described therapeutic successes, CT and X-ray examinations for more accurate
determination of possible remineralization are unnecessary.
If a lesion progresses, then embolization can be repeated, as was the case of the
two patients in our series. As shown in post-interventional MRIs, repeated embolization
in both cases achieved local tumor control. Our results demonstrate that embolization
can be effectively used even for very large ABCs. In the case of recurring bladder
or rectal dysfunction as well as apparent paresis, embolization can be utilized for
preoperative reduction in bleeding; however, this should not result in unnecessary
delay of prompt surgical decompression. Resection of the ABC is not indicated in such
cases, however, since embolization can inhibit further growth. If interventional treatment
of the ABC is required, regular MRI follow-up is indispensable. In this way the success
of the therapy, or, if necessary, the need for further therapeutic actions can be
detected promptly.
A basic limitation of this study is the small size of the patient cohort; however
this can be ascribed to the low incidence of sacral ABC. A further limitation is the
lack of a comparative cohort. Due to the above-mentioned possible treatment complications,
delayed action or surgery is not justified, however.
In the case of five of six patients, the follow-up examination time frame is greater
than two years; for patient number six, this ended after eight months following surgical
decompression. In this case, as well, MR images exhibit local tumor control. Despite
these limitations, there are promising results; in our study cohort, transarterial
embolization represents a safe and effective therapeutic approach which in our clinic
has shown great value in the interdisciplinary treatment of aneurysmal bone cysts
of the sacrum.
Clinical Relevance of the Study
-
Transarterial embolization can be successfully employed for the treatment of aneurysmal
bone cysts at problematic locations such as the sacrum.
-
In addition to local tumor control, transarterial embolization results in pain reduction.
-
Complication-prone operations for the purpose of local tumor control have been avoidable
in our cohort by using transarterial embolization.
-
Even though an ABC has shown progression, repeated embolization can achieve local
tumor control.
