Rom J Morphol Embryol 2014, 55(3):977981

RJME
CASE REPORT Romanian Journal of
Morphology & Embryology
http://www.rjme.ro/

Aneurysmal bone cyst clinical and morphological aspects

RADU RDULESCU1,2), ADRIAN BDIL2), ROBERT MANOLESCU2), MARIA SAJIN1,3), ION JAPIE2)
1)
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
2)
Department of Orthopedic Surgery, Bucharest University Hospital, Romania
3)
Department of Pathology, Bucharest University Hospital, Romania

Abstract
Aim: To assess the results of surgical treatment in aneurysmal bone cysts. Materials and Methods: 31 patients with aneurysmal bone cysts
underwent surgical treatment in our department. In almost half of cases, the lesion was located in the femur. In 12 cases, a pathological
bone fracture was the first clinical sign. The treatment consisted in curettage, abrasion of the cavity inner walls using a motorized burr and
filling with morsellized bone grafts (autografts allografts) or bone substitutes (four cases). Microscopically, the diagnosis relies on cystic
spaces filled with blood, divided by fibrous septae consisting in immature bone trabeculae, hemosiderin filled macrophages and fibroblasts.
We performed multiple bioptic probes from different levels of the lesion. Results: Macroscopically, the osseous lesion appeared as a multi-
loculated blood-filled cavity (cavities separated by septa) in 30 (96.77%) cases and as a solid tumor in one (3.23%) case. At 12 months
after surgery, grafts osteointegration was present in 24 cases. At an average follow-up time of six years and four months, refilling with bone
grafts was necessary in two cases and no local recurrence was observed. Conclusions: Aneurysmal bone cyst is most frequent in the
second decade of age. Its prevalence in female gender is double compared to the male gender. The positive diagnosis relies on the
histopathological examination. Because of the strong relationship with a number of precursor lesions (giant cell tumor, fibrous dysplasia,
non-ossifying fibroma, chondroblastoma, osteoblastoma) multiple bioptic probings are mandatory, in order to diagnose, if possible, a primary
lesion, which may modify the therapeutic attitude. Treatment by curettage, abrasion of the cavity inner walls and filling with morsellized grafts
has very good results. The risk of recurrence is very low.
Keywords: aneurysmal bone cyst, curettage, bone grafting.

Introduction t(16; 17)(q22;p13), while Oliveira et al. [5, 6] showed

that this cyst can be considered as a clonal neoplastic
Aneurysmal bone cyst is an expansive benign bone disorder, the genes involved being USP6 and CDH11.
lesion, which appears like a group of intraosseous Cytogenetic studies have shown that many aneurysmal
cavities lacking endothelial membrane and containing bone cysts are clonal proliferations due to activation of an
blood. Peak incidence is recorded in the second decade oncogene located on chromosome 17. Oncogene activation
of life, 80% of them occurring in patients less than 20 can be achieved through several mechanisms involving the
years [1]. Gender distribution is males/females 1:1.3, rearrangement of genetic material located on chromosome
and the incidence in the general population is 0.14/ 17. Most often, balanced translocations are found between
100 000 [2], representing about 1% of total bone tumors.
the short arm of chromosome 17 and the long arm of
Most frequently, it is found at proximal and distal
chromosome 16, but these translocations can also occur
metaphysis of the femur and the proximal metaphysis of
between chromosome 17 and other chromosomes.
tibia, but can affect almost any bone segment in the body.
The aneurysmal bone cyst can be secondary to benign
Other frequent locations are the humerus, the vertebrae
tumors: giant cell tumor (the most frequent association),
and the pelvic bones. 5060% of cases involve long bones
chondroblastoma, chondromyxoid fibroma, osteoblastoma
of the limbs (lower limb 40% and upper limb 20%,
or fibrous dysplasia or malignant tumors: osteosarcoma,
respectively) and in 2030% of cases the lesion is located
chondrosarcoma and hemangioendothelioma.
in the spine.
The aim of our study is to assess the medium term
Although it was described as early as 1942 by Jaffe
results of surgical treatment in aneurysmal bone cysts.
and Lichtenstein [3], its etiopathogenesis is still uncertain,
with vascular, trauma and genetic factors being the
involved. This condition may be primitive or secondary. Patients and Methods
The occurrence of the primary aneurysmal cyst is classically Between 2001 and 2010, 31 patients with aneurysmal
explained because of a local circulatory disorder leading bone cysts underwent surgical treatment in our department.
to increased venous pressure with subsequent dilation Gender ratio was 21 females/10 males. The mean age of
and rupture of the local vascular network. Recent genetic patients was 23 years (extremes: 1541 years). In almost
research conducted by Panoutsakopoulos et al. [4] and half of cases (15), the lesion was located in the femur
Oliveira et al. [5, 6] have demonstrated a genetic compo- (eight in the proximal metaphysis and seven in the distal
nent in the etiology of primitive aneurysmal cyst. Thus, one). Other recorded sites in our series were: distal radius
Panoutsakopoulos et al. [4] showed an association between metaphysis (four cases), proximal humeral metaphysis
primitive aneurysmal cyst and a chromosomal translocation (three cases), proximal end of the tibia (eight cases),

ISSN (print) 12200522 ISSN (on-line) 20668279

978 Radu Rdulescu et al.
calcaneus (one case). In 12 cases, a pathological bone Results
fracture was the first clinical sign. The treatment consisted
in curettage of the lesion, abrasion of the cavity inner Important postoperative bleeding was recorded in six
walls by a motorized burr and filling with morsellized cases. At 12 months after surgery, grafts osteo-integration
bone grafts (autografts allografts) (Figure 1) or bone was present in 24 cases. At an average follow-up time of
substitutes (four cases). Autografts were used in all six years and four months, refilling with bone grafts was
bone graft cases, while allografts in eight patients only. necessary in two cases and no local recurrence was observed.
In eight cases, a lavage of the cyst cavity with 100% At one year after surgery, no clinical symptoms were
alcohol was performed. Osteosynthesis was associated in present. Full postoperative recovery of the operated limb
22 cases. To access the lesion, we performed a window was achieved, in average, at four months. Macroscopically,
osteotomy of the thinned cortex. Inside the bone, the lesion the osseous lesion appeared as a multi-loculated blood-
appears as a cavity filled with blood and divided by thin filled cavity (cavities separated by septa) in 30 (96.77%)
fibrous walls. We performed multiple bioptic probings cases (Figure 2) and as a solid tumor in one (3.23%) case.
from different levels of the lesion.

Figure 2 Aneurysmal
bone cyst: macroscopic
intraoperative view.

Figure 1 Aneurysmal bone cyst in the proximal femoral

metaphysis preoperative and postoperative X-ray views:
curettage and grafting with morsellized osseous auto-grafts,
osteosynthesis with DHS (dynamic hip screw), bone window
fixed with screw.

Microscopically, the diagnosis relies on cystic spaces fibroblasts, myofibroblasts and hystiocytes. Immunohisto-
filled with blood (Figure 3), divided by fibrous septa chemical studies demonstrate the absence of endothelial
consisting in immature bone trabeculae, giant cells cells at this site.
(Figure 4), hemosiderin filled macrophages and fibroblasts. Intralesional fibrous septa contain reactive osteoid
At microscopic examination, blood-rich multi-locular material with osseous trabeculae, lined with plump osteo-
cavernous spaces of variable dimensions were observed, blasts (Figures 5 and 6). The osteoid material is richer at
delineated by fine membranous septa composed of fibrous the peripheral area of the lesion. Sometimes, the osteoid
tissue with thin-walled capillaries, hystiocytes, osteoclast- material has a fibrillar, linear pattern, with less minera-
like giant cells and inflammatory cells. The intratumoral lization, whereas inside the fibrous septa within the
septa, at the boundaries between cavernous spaces, display tumor, the osteoid material has a parallel arrangement.

Figure 3 Aneurysmal bone cyst: bone tissue left, cavity Figure 4 Aneurysmal bone cyst. Bone tissue, hemorrh-
with sanguine content right. HE staining, 100. agic zones, giant cells. HE staining, 200.
 Aneurysmal bone cyst clinical and morphological aspects 979

Figure 5 Periphery of aneurysmal bone cyst (ABC) Figure 6 Reactive osseous tissue. Detail image: osteo-
trabeculate osseous tissue. Zone of reactive bone tissue blastic proliferation. HE staining, 100.
and peritumoral zone. HE staining, 40.

Chondroid or myxohyaline materials were found six Multiplanar slices obtained by complex imaging
cases in the fibrous septa. These areas can sometimes be examinations (CT, MRI) should be carefully studied
numerous, with variable inner calcifications. in order to identify any concomitant tumor (benign or
Giant multinucleated osteoclast-like cells can be also malignant), knowing that about 30% of aneurysmal bone
found in various numbers, which differ from one tumor to cysts are secondary to other tumors. Bone scintigraphy is
another and from one tumor area to another. rarely used for diagnosis, because it lacks specificity. The
Mitosis (found in two cases) can sometimes become lesion hypercaptures the radiotracer in the periphery,
numerous, especially in regions with rich osteoid material, while the core and adjacent bone capture it normally.
at previous biopsy sites or pathological fracture sites. Scintigraphy examination may reveal a lesion not yet
Cellular atypia, cellular pleomorphism or hyperchromasia, manifested clinically and indicates the area to be explored
as cytological markers of malignancy, were absent. by other imaging methods.
The solid variant of ABC does not displayed vascular In our study, antero-posterior and lateral view radio-
pseudocystic spaces with fibroblast proliferation and graphic examinations were conducted in all cases (100%),
osteoclastic-like multinucleated giant cells, hemorrhagic CT scan in 28 (90.32%) cases and MRI in 15 (48.39%)
areas or foam cells with hemosideremic pigmentation. cases.
Trabeculae of reactive osseous tissue are always present The aneurysmal bone cysts are primitive or second-
and have a rather uniform distribution inside the tumor. dary to giant cell tumor, chondroblastoma, osteoblastoma
In the case where the lesion appeared macroscopically and fibrous dysplasia. All aneurysmal cysts in our series
as a solid tumor, the histopathological diagnosis was based were primitive.
on a combination of fibroblastic proliferation, osteoid Definitive diagnosis was assessed by histopathology
production and fibromyxoid elements. exam. Macroscopically, the cyst appears as a cavity
with septa made of thin fibrous walls, filled with friable
Discussion clots. Overlying cortical bone is thin and fragile.
Histopathologically, there are two varieties classic
The aneurysmal bone cyst is an expansive and lytic cavitary form and solid form. In the cavitary form (95%
bone lesion leading to cortical bone thinning, without of cases), the tumor appears as a group of blood-filled
exceeding it. Symptoms consist of pain, which progress- cavities separated by septa containing bone trabeculae
ively worsens and becomes persistent, deformation of (immature bone or osteoid tissue), stromal spindle cells,
the bone segment, the latter being visible if the bone fibroblasts, histiocytes, hemosiderin filled macrophages,
is located superficially or occurrence of pathological capillaries and giant cells osteoclasts. There is no
fractures. endothelial membrane. Mitoses are present, sometimes
Radiological examination shows a radiolucent in large numbers. No atypical mitoses are observed. In
lesion, well delimitated by a thin sclerotic margin which approximately one third of cases, the bone is basophilic,
can be polylobated, containing intralesional septa. The taking the aspect of blue bone; it is not a specific
lesion is mostly eccentric situated in the metaphyseal lesion, as this can be found in other conditions, too. In
area of long bones. The cortex is thinned, but generally the solid form (5%), one can observe fibroblastic proli-
intact, lacking any periosteum reaction. Computed feration, osteoid production and fibromyxoid elements
tomography scan allows the exact three-dimensional with a tendency to calcification.
location and measuring of the tumor and may show the Concerning immunochemistry, monocyte and macro-
cavitary-septa structure of this pseudotumoral finding. phage markers are present in most stromal cells and some
MRI shows a fluid content and multiple intracavitary giant cells. The stromal cells will stain with myeloid
fluid-fluid levels (serum/blood). The cyst shows intense macrophage markers (MAC387 and HAM56), muscle
signal in T1 images and intermediate or decreased specific markers, fibriohistiocytic markers and protease
signal in T2 images. inhibitors (1-antitrypsin and 1-antichymotrypsin) [5].
980 Radu Rdulescu et al.
The aneurysmal bone cyst can be secondary to a insulin-like growth factor-I were detectable in aneurysmal
number of bone tumors: giant cell tumors, chondro- bone cysts and were mainly localized in multinucleate
blastoma, fibrous histiocytomas, chondromyxoid fibromas, giant cells. The levels of insulin-like growth factor-I in
fibrous dysplasia or osteosarcoma. The pathologist must normal human bone tissue are negligible.
know the radiological appearance of these tumors in In an immunohistochemistry study of the vascular
order to determine if the aneurysmal bone cyst is a markers in aneurysmal bone cyst, Shinde et al. [9]
primary or secondary lesion. demonstrated that factor 8 is present at the edge of ABC
The most difficult differential diagnosis of the cavities in almost all cases, while VEGF-C, GLUT-1
aneurysmal bone cyst is with the telangiectatic osteo- and smooth muscle actin are present in approximately
sarcoma, which has many clinical, radiological and even half the cases. D2-40 and CD34 are present at the edge
histological similarities. The distinction between the two is of the cavities in some cases. All this facts, suggest that
made by histopathological examination, the telangiectatic the vascular factor and vascular trauma are involved in
osteosarcoma having the characteristics of a malignant the pathogenesis of the aneurysmal bone cyst.
tumor within the hemorrhagic membranes (pleomorphic In our series, the treatment of the lesion consisted
cells producing osseous or osteoid tissue and atypical of creating an approximately rectangular cortical lid,
mitoses) under microscopic examination. In the aneurysmal harvesting intracavitary tissue from several areas, thorough
bone cyst, atypical mitoses are absent. However, cellular cavity curettage, filling it with morsellised bone grafts,
atypia, pleomorphism and hyperchromasia are found closing the lid to maintain bone grafts within the cavity,
only with osteosarcoma; in addition, the tumor margins and fixation, in those cases where we considered that
are ill defined, unlike in the case of an ABC where the mechanical strength of the segment might be compromised
tumor has an eggshell-like, thin cortical. and needs reinforcement. Intraoperative macroscopic
The giant cell tumor (GCT) displays large multi- inspection revealed cavities containing friable blood
nucleated cells. In the case of ABC however, nuclei are clots. We inspected the bone limits of the cyst and the
more numerous than in the GCT and they are more adjacent bone to detect a possible bone tumor, which
centrally situated. Moreover, ABC has a much more could lead to development of a secondary aneurysmal
fibrous/fibroblastic stroma. bone cyst.
Giant cell reparative granuloma can be mistaken for In order to achieve a correct curettage of the bone
a solid form of ABC. Anyway, giant cell reparative cavity, especially towards its margins, we used a variable
granuloma has a specific localization (jawbone), with speed burr with heads of various sizes [10]. The remaining
limited areas of osteoid tissue. cells are removed by local application of pure alcohol
The unicameral osseous cyst consists on a clear (eight cases in our group), phenols or liquid nitrogen,
serosanguinolent lesion, without intratumoral fibrous which also decreases the risk of relapse [11].
septa. However, its differential diagnosis following a Cavity filling was achieved with morsellized auto-
fracture can be difficult due to hemorrhage, the presence grafts. This avoids the risk of contamination with viral
of reactive osseous tissue and multinucleate giant cells. germs from the allografts donor, providing faster osteo-
The osseous hemangioma is a lesion in which vascular integration. When the residual cavity was large, additional
spaces contain endothelial cells, and the osseous trabe- morsellized allografts were necessary (eight cases). During
culae are mature, without displaying a reactive pattern. follow-up, there were no statistically significant differ-
Oliveira et al. [6] identified an association between ences between autografts and allografts osteointegration,
the aneurysmal bone cyst and clonal chromosome band although allografts have been used exclusively in larger
17p13 translocations that place the USP6 (TRE2 or defects, but mixed with autografts [12].
TRE17) oncogene under the regulatory influence of the Another method of filling the residual cavity is by
highly active CDH11 promoter. They found CDH11 and/or using either bone substitutes (four patients in our group),
USP6 rearrangements in 69% of cases with primitive either acrylic cement. The persistence of bone substitutes
aneurysmal bone cyst. These USP6 and CDH11 rearran- was detected in all postoperative radiological controls
gements were present in the spindle cells and were performed in those cases.
absent in multinucleated giant cells, inflammatory cells, Other treatment options include lesion nutritional
endothelial cells or osteoblasts. The translocations were vessels embolization, percutaneous injection of acrylic
also absent in the entire secondary aneurysmal bone cements or agents capable of inducing fibrosis, segmental
cyst. In his opinion, the primary aneurysmal bone cysts resection with reconstruction [12], percutaneous sclero-
are mesenchymal neoplasms, while the secondary ones therapy with Polidocanol [13], percutaneous Doxycycline
are non-aneurysmal bone cysts neoplasms that mimic treatment [14] and Denosumab administration [15]. These
the morphology of the aneurysmal bone cyst. In another methods are used mainly in cysts located in the pelvis
study [7], the same authors demonstrated the implication or vertebrae, which are surgically less accessible or
of the USP6 oncogene in the pathogenesis of the aneu- inaccessible at all.
rysmal bone cyst, by showing how aneurysmal bone cyst Complete functional rehabilitation of the segment
variant translocations upregulate USP6 transcription by was achieved on average at four months postoperatively,
promoter swapping with the ZNF9, COL1A1, TRAP150, while one year postoperatively patients were asymptomatic
and OMD genes. and fully reintegrated socially and professionally.
Leithner et al. [8], using immunohistochemistry and We did not record any local recurrence, but in two
in situ hybridization, showed that insulin-like growth cases with large lesions, cavity refilling using bone allo-
factor-I (IGF-1)or specific mRNA sequences encoding for grafts was required, due to partial resorption and poor
 Aneurysmal bone cyst clinical and morphological aspects 981
osteointegration of the initial grafts. Further evolution [4] Panoutsakopoulos G, Pandis N, Kyriazoglou I, Gustafson P,
Mertens F, Mandahl N, Recurrent t(16;17)(q22;p13) in
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which becomes more fragile (leading to pathological USP6 and CDH11 oncogenes identify the neoplastic cell in
fractures subsequent to minimal trauma) and symptomatic primary aneurysmal bone cysts and are absent in so-called
(pain is the main revealing symptom). Buraczewski and secondary aneurysmal bone cysts, Am J Pathol, 2004, 165(5):
17731780.
Dabska [16] have proposed three evolutive stages: initial
[7] Oliveira AM, Perez-Atayde AR, Dal Cin P, Gebhardt MC,
phase osteolysis without peculiar findings; growth Chen CJ, Neff JR, Demetri GD, Rosenberg AE, Bridge JA,
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3843.
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majority of aneurysmal bone cyst appears as a multi- and high-speed burring sufficient treatment for aneurysmal
loculated blood-filled cavity, while the form of solid bone cysts? Clin Orthop Relat Res, 2014, Jul 22.
tumor is very rare. The positive diagnosis relies on the [11] Reddy KI, Sinnaeve F, Gaston CL, Grimer RJ, Carter SR,
Aneurysmal bone cysts: do simple treatments work? Clin
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[15] Lange T, Stehling C, Frhlich B, Klingenhfer M, Kunkel P,
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Corresponding author
Adrian Bdil, MD, Department of Orthopedic Surgery, Bucharest University Hospital, 169 Independenei Avenue,
Sector 5, 050098 Bucharest, Romania; Phone +40722516 470, e-mail: [email protected]

Received: December 15, 2013

Accepted: September 1, 2014