Clinical Imaging 62 (2020) 23–32

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Clinical Imaging
journal homepage: www.elsevier.com/locate/clinimag

Musculoskeletal and Emergency Imaging

Secondary aneurysmal bone cysts and associated primary lesions: imaging T

features of 49 cases
Luis B. Gutierreza,1, , Thomas M. Linka, Andrew E. Horvaib, Gabby B. Josepha,
⁎

Richard J. O'Donnellc, Daria Motamedia

a
Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America
b
Department of Pathology, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America
c
Department of Orthopaedic Surgery, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, United States of America

ARTICLE INFO ABSTRACT

Keywords: Purpose: To describe the imaging, anatomic, and clinical features of a series of secondary aneurysmal bone cysts
Aneurysmal bone cyst (ABC) and to ascertain their most commonly associated primary bone lesions.
Musculoskeletal imaging Methods: Forty-nine cases of histopathologically proven secondary ABCs were retrospectively reviewed.
Bone tumor Demographic data and clinical history were obtained. Radiographic, computed tomographic, magnetic re-
Giant cell tumor
sonance, and nuclear medicine imaging were analyzed. Lesion location, imaging characteristics, and associated
Chondroblastoma
Fibrous dysplasia
primary lesions were documented. Linear regression analysis and Chi-squared testing was performed for sta-
Osteoblastoma tistical analysis.
Osteosarcoma Results: Twenty-four males and 25 females were included, with an age range of 8—79 years (mean 29.7 + −
4.5 years). Eleven types of primary bone lesion were identified, with giant-cell tumor (n = 17, 35%), chon-
droblastoma (n = 11, 22%), fibrous dysplasia (n = 6, 12%), osteoblastoma (n = 4, 8%) and osteosarcoma
(n = 4, 8%) being the most frequent. The lesions involved chiefly the long bone epiphyses (n = 25, 51%).
Secondary ABC imaging findings and locations most closely approximated those of their primary counterparts,
although fluid-fluid levels were seen at a higher frequency than previously reported in primary chondroblastoma
(9/11, 82%), fibrous dysplasia (2/6, 33%), osteoblastoma (4/4, 100%), osteosarcoma (3/4, 75%), and chon-
dromyxoid fibroma (1/2, 50%).
Conclusion: The most common primary lesions associated with secondary ABC were giant cell tumor and
chondroblastoma, located in the long bone epiphyses. The majority of the secondary ABCs demonstrate pre-
dominant imaging characteristics typical of the primary bone lesions, but with a higher presence of fluid-fluid
levels.

1. Introduction
Aneurysmal bone cyst (ABC), first described in the literature by
Jaffe and Lichenstein in 1942 [1], is a benign, expansile, osteolytic
lesion composed of blood-filled spaces segregated by connective-tissue
septa, mostly involving the long bones and spines of children and young
adults [2–10]. The lesion develops either de novo as a true mesench-
ymal neoplasm, termed a primary ABC, or secondary to a pre-existing
bone lesion, termed a secondary ABC [9,11–14]. Secondary ABCs can
be morphologic mimics of primary ABCs, but lack the USP6 and CDH11
gene abnormalities frequently seen in primary ABCs and likely develop
as a common pathophysiologic endpoint of various types of non-ABC
primary bone lesions [11]. Secondary ABC demonstrates similar pa-
thologic characteristics as a primary ABC, but has further histologic
findings indicating the presence of an additional coexisting lesion [2].
Approximately 70% of ABC cases are primary, and 30% are secondary
[2–4,10]. Secondary ABCs have previously been associated with a
variety of benign, borderline and malignant primary bone lesions in-
cluding giant cell tumor, chondroblastoma, osteoblastoma, fibrous
dysplasia, Langerhans cell histiocytosis, hemangioma, nonossifying fi-
broma, and osteosarcoma [2–5,10,11].
Although several studies have described the radiologic, pathologic,
and clinical characteristics of primary ABCs, there is a paucity of this
information in the literature regarding secondary ABCs [2,5,10,11,15].

Corresponding author at: Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave., Room M391, Box 0628,
⁎

San Francisco, CA 94143, United States of America.

E-mail address: lbgutier@alumni.stanford.edu (L.B. Gutierrez).
1
Present address: 100 West California Blvd, Pasadena, CA 91105.

https://doi.org/10.1016/j.clinimag.2020.01.022
Received 28 October 2019; Received in revised form 13 January 2020; Accepted 27 January 2020
0899-7071/ © 2020 Elsevier Inc. All rights reserved.
L.B. Gutierrez, et al.
As a result, diagnosis of secondary ABC may still be challenging and
biopsy misleading [16,17]. One potential diagnostic pitfall is the mis-
interpretation of a secondary ABC as a primary lesion potentially
missing an underlying malignancy. In particular, small biopsy speci-
mens and inadequate imaging increase the potential for misdiagnosis.
In this situation, the role of a radiologist with expertise in muscu-
loskeletal imaging is crucial in ensuring that there is optimal radiologic-
pathologic correlation and accurate diagnosis.
The purpose of this study is to describe the imaging, anatomic, and
clinical features of a series of pathologically proven secondary ABCs, to
ascertain their most common associated primary bone lesions, and to
highlight typical imaging features, facilitating radiologic-pathologic
correlation efforts.
2. Materials and methods
2.1. Patient cohort
This retrospective study is in compliance with the Health Insurance
Portability and Accounting Act and was approved by our institutional
review board. Our institution's pathology database was retrospectively
analyzed and all reviewable cases of pathologically proven secondary
ABCs were compiled since 1988. Exclusion criteria included lack of
diagnostic radiologic imaging prior to tissue diagnosis, more definitive
follow-up pathology demonstrating a diagnosis other than secondary
ABC, or final pathologic diagnosis rendered at another institution.
Patient age at time of diagnosis, gender, relevant medical comorbid-
ities, presenting symptoms, and available pre-biopsy radiologic imaging
were recorded, as detailed in the electronic medical record. A total of
49 subjects fulfilled all of the inclusion and exclusion criteria of this
study.
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Clinical Imaging 62 (2020) 23–32
Fig. 1. 14-year-old girl with a history of shoulder
pain secondary to a humeral head chondroblastoma
with secondary ABC. The lesion was treated with
curettage. Low magnification photomicrograph of
the surgical specimen demonstrates chondro-
blastoma component (arrow) composed of plaque-
like fibrochondroid stroma, ovoid mononuclear cells
with eccentric cytoplasm and stippled calcifications.
Secondary ABC component (arrowhead) is composed
of collagenous fibrous septae containing spindle
cells, foam cells, hemosiderin and osteoclast-type
giant cells.
2.2. Imaging and image analysis
Using our institution's picture archiving and communication system
(PACS), each patient's radiologic images were reviewed in consensus by
two fellowship trained musculoskeletal radiologists (25 years and
7 years of experience in musculoskeletal radiology). Because of the long
time period over which cases were retrospectively collected, a wide
range of radiographs (in 39/49 cases), computed tomographies (CT) (in
22/49 cases), magnetic resonance (MR) imaging studies (in 39/49
cases), and nuclear medicine studies (in 17/49 cases) were available for
pre-operative analysis. Specific imaging characteristics were docu-
mented for each lesion systematically, including lesion location, size,
margin definition, margin sclerosis, expansile nature, cortical thinning,
fracture, periosteal reaction, bone marrow edema, internal architecture
including internal matrix, septations, or trabeculations, soft-tissue
mass, fluid-fluid level on cross-sectional imaging, contrast enhance-
ment, radiopharmaceutical uptake, and T1/T2/proton density signal
intensity on MR imaging. The signal intensities on MR were classified as
hypo-, iso-, and hyperintense in comparison with muscular signal in-
tensity. In cases of heterogeneous signal intensities, the predominant
signal intensity of the lesion, defined as signal intensity of more than
50% of the lesion, was recorded.
2.3. Pathological diagnosis
The pathologic diagnoses of the primary bone lesions and of sec-
ondary ABC, respectively, were established histologically based on
standard criteria [18]. The diagnoses were confirmed by a pathologist
with expertise in bone pathology. Cases were classified histologically by
their primary tissue diagnosis, anatomically by the main bone involved
(e.g., proximal humerus, distal femur), and further anatomically by the
L.B. Gutierrez, et al. Clinical Imaging 62 (2020) 23–32

Table 1
Secondary aneurysmal bone cyst, summary table.
Case Histology Main bone, sub-location center Gender Age (years) Size (cm) Imaging

1 Giant-cell tumor Femur, distal epiphysis M 29 6×8×5 XR

2 Giant-cell tumor Femur, distal epiphysis M 57 8×5x7 XR, CT, MR, PET
3 Giant-cell tumor Femur, distal epiphysis M 25 4×3×4 XR
4 Giant-cell tumor Femur, distal epiphysis F 31 6×6×8 XR, CT, PET
5 Giant-cell tumor^ Femur, distal epiphysis F 35 2×4×7 XR, MR
6 Giant-cell tumor Tibia, proximal epiphysis F 37 5×4×6 XR, MR
7 Giant-cell tumor Tibia, proximal epiphysis F 23 4×4×5 XR, MR, BS
8 Giant-cell tumor Tibia, proximal epiphysis M 53 5×5×5 XR, CT, MR, BS
9 Giant-cell tumor Tibia, proximal epiphysis F 21 4×4×5 XR, CT, MR
10 Giant-cell tumor Tibia, proximal epiphysis F 29 5×6×8 XR, CT, MR, BS
11 Giant-cell tumor Tibia, proximal epiphysis M 56 6×5×5 XR, MR
12 Giant-cell tumor Humerus, proximal epiphysis M 25 5×5×6 XR, MR, BS
13 Giant-cell tumor Humerus, proximal epiphysis M 22 4×4×6 XR, MR
14 Giant-cell tumor Radius, distal epiphysis M 31 3×3×4 XR
15 Giant-cell tumor Ulna, distal epiphysis M 39 3×3×5 XR, MR, BS
16 Giant-cell tumor Pelvis, sacrum M 24 4×3×2 CT, MR
17 Giant-cell tumor Patella, entire bone M 27 2×4×4 XR, MR
18 Chondroblastoma Femur, epiphysis M 18 3×3×4 XR, CT, MR, BS
19 Chondroblastoma Femur, greater trochanter F 26 8×4×4 XR, MR, BS
20 Chondroblastoma Femur, greater trochanter F 16 4×2×2 XR, MR
21 Chondroblastoma Tibia, proximal epiphysis F 13 3×4×3 XR, MR
22 Chondroblastoma Tibia, distal epiphysis F 29 5×5×6 XR, CT, MR
23 Chondroblastoma Humerus, greater tuberosity F 14 3×2×2 XR, MR
24 Chondroblastoma Humerus, distal epiphysis M 27 2×3×2 XR, MR, BS
25 Chondroblastoma Pelvis, ischiopubic synchondrosis F 16 4×2×1 XR, CT, MR
26 Chondroblastoma Talus, medial aspect M 26 3×3×3 XR, CT, MR
27 Chondroblastoma Talus, medial aspect M 28 4×3×2 CT, MR
28 Chondroblastoma Metacarpal, proximal epiphysis M 18 4×4×5 XR
29 Fibrous dysplasia Femur, mid diaphysis F 24 2 × 2 × 17 XR, MR, BS
30 Fibrous dysplasia Rib, anterior 1st and 2nd F 38 9 × 5 × 10 XR, CT
31 Fibrous dysplasia Rib, lateral 4th and 5th M 37 6×2×6 CT
32 Fibrous dysplasia Metacarpal, proximal diaphysis F 13 2×2×2 XR, MR, BS
33 Fibrous dysplasia Pelvis, ilium M 31 3×2×3 XR, CT, MR
34 Fibrous dysplasia~ Cranium, parietal bone M 21 6×6×6 CT, MR
35 Osteoblastoma Metatarsal, entire diaphysis F 11 5×2×2 XR, MR
36 Osteoblastoma Talus, anterosuperior aspect F 24 3×2×3 XR, CT, MR
37 Osteoblastoma` Cranium, sphenoid bone F 25 7×4×6 CT, MR
38 Osteoblastoma Thoracic spine, posterior elements M 15 3×4×3 CT, MR, BS
39 Osteosarcoma Femur, distal metaphysis F 20 13 × 7 × 4 XR, CT, MR, PET, BS
40 Osteosarcoma Pelvis, ilium F 79 13 × 20 XR
41 Osteosarcoma Cranium, temporal bone M 43 6×4×7 MR
42 Osteosarcoma* Femur, distal metaphysis F 32 9 × 7 × 10 XR, MR
43 Chondromyxoid fibroma Tibia, proximal metaphysis M 65 56 × 5 XR, MR, BS
44 Chondromyxoid fibroma Cranium, occipital bone M 8 1×1×1 CT, MR
45 Ossifying fibroma Mandible, ramus F 67 4×5×5 CT
46 Hemangioma Calcaneus, anterolateral aspect M 23 4×4×3 XR, MR, PET
47 Epithelioid hemangioma Fibula, distal epiphysis F 8 2×1×2 MR
48 LCH Femur, proximal diaphysis M 11 2×2×5 XR
49 Osteonecrosis Femur, proximal epiphysis M 63 4 × 6 × 17 XR, CT, MR, PET

Note. — M = Male, F = Female, ^ABC in lesion recurrence, measured largest of multiple lesions, ~McCune-Albright syndrome, ` Aggressive osteoblastoma subtype,
*ABC in lesion recurrence, LCH = Langerhans cell histiocytosis, XR = Radiograph, CT = Computed tomography, MR = Magnetic resonance, BS = Bone scan,
PET = Positron emission tomography.

sub-location center (e.g., epiphyseal, diaphyseal, metaphyseal). Mean the 11 lesion types; if only one case example was available for a type of
radiologic lesion size was calculated for each type of primary bone le- primary lesion, the largest measured diameter was used.
sion by first obtaining the largest measured diameter for each of the 49
cases, then using these diameters to obtain a mean diameter for each of

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L.B. Gutierrez, et al. Clinical Imaging 62 (2020) 23–32

Table 2
Secondary ABC case and demographics summary.
Mean lesion size Age range Mean age

Histology Cases Male Female (cm), ± SD (years) (years)

Giant-cell tumor 17 (35%) 9 (18%) 8 (16%) 5.8 ± 1.5 21–57 33.2

Chondroblastoma 11 (22%) 5 (10%) 6 (12%) 4.4 ± 1.4 13–29 21
Fibrous dysplasia 6 (12%) 3 (6%) 3 (6%) 7.3 ± 5.0 13–37 27.3
Osteoblastoma 4 (8%) 1 (2%) 3 (6%) 4.8 ± 1.5 11–25 18.3
Osteosarcoma 4 (8%) 1 (2%) 3 (6%) 12.5 ± 4.8 20–79 43.5
Chondromyxoid fibroma 2 (4%) 2 (4%) 0 3.5 ± 2.5 8–65 36.5
Ossifying fibroma 1 (2%) 0 1 (2%) 5 67 –
Hemangioma 1 (2%) 1 (2%) 0 4 23 –
Epithelioid hemangioma 1 (2%) 0 1 (2%) 2 8 –
Langerhans cell histiocytosis 1 (2%) 1 (2%) 0 5 11 –
Osteonecrosis 1 (2%) 1 (2%) 0 17 63 –
Total 49 24 25 6.1 8–79 29.7

Note.—Mean lesion sizes were calculated for each type of primary bone lesion by averaging the largest measured diameters for each primary lesion type. If only one
case example was available, the largest measured diameter was provided.
SD = Standard deviation.

Fig. 2. 57-year-old man presented with a history of

progressive knee pain due to giant-cell tumor with
secondary ABC. Frontal radiograph of the distal
femur (a) demonstrates a well-defined lytic lesion
centered at the medial aspect of the distal femoral
epiphysis, lacking a sclerotic border. Axial positron
emission tomography image through the distal fe-
murs (b) demonstrates relative radiopharmaceutical
uptake in the left distal femur at the site of the giant-
cell tumor. Axial CT image of the distal femur on
bone window (c) demonstrates a well-defined, lytic
lesion. Coronal proton density weighted fat saturated
MR image of the distal femur (d) demonstrates a
well-defined hyperintense lesion centered in the
epiphysis and extending to the subchondral region,
containing internal septations, and surrounded by
moderate periosteal reaction and bone marrow
edema. Axial proton density weighted fat saturated
MR image of the distal femur (e) demonstrates fluid-
fluid levels within the lesion (arrow).

26
L.B. Gutierrez, et al.
3. Statistical analysis
Statistical analysis was performed using STATA version 14 software
(StataCorp LP, College Station, TX). The statistical significance
threshold was set at a p value less than 0.05. Lesion volumes were
calculated by multiplying transverse, anteroposterior, and craniocaudal
lengths of the lesions. Linear regression analysis was used to quantify
the associations between lesion type and (a) age at diagnosis and (b)
lesion volumes, as well as to quantify the associations between patient
ages and lesion volumes. Chi-squared tests were used to assess differ-
ences in the distribution between lesion type and (a) gender (b) lesion
location (c) presence of a well-defined margin (d) presence of margin
sclerosis (e) presence an expansile lesion (f) presence of cortical thin-
ning (g) presence of a fracture (h) presence of periosteal reaction (i)
presence of bone marrow edema (j) presence of internal architecture (k)
presence of a soft tissue mass and (l) presence of fluid-fluid levels.
4. Results
Between August 1988 and July 2016 (28 year time period), 81
patients underwent bone tissue sampling with an initial diagnosis of
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Clinical Imaging 62 (2020) 23–32
Fig. 3. 16-year-old female patient presented with a
9-month history of left hip pain due to chondro-
blastoma with secondary ABC. Frontal radiograph of
the proximal femur (a) demonstrates a well-defined
lytic lesion centered at the greater trochanter (an
epiphyseal equivalent), with a mildly sclerotic
border. Sagittal (b) and axial (c) proton density
weighted fat saturated MR images of the proximal
femurs demonstrate a well-defined lesion centered in
the left greater trochanter, containing internal sep-
tations, surrounded by mild periosteal edema and
bone marrow edema compared to the contralateral
side, and containing fluid-fluid levels (arrows).
secondary ABC. A total of 32 of these patients were excluded either
because of a lack of diagnostic radiologic imaging prior to pathologic
diagnosis of secondary ABC (n = 24), more definitive follow-up pa-
thology demonstrating a diagnosis of primary rather than secondary
ABC (n = 4), more definitive follow-up pathology demonstrating a lack
of secondary ABC (n = 2), or because final histologic diagnosis was
performed at an outside institution (n = 2).
The final study population comprised of 25 females (age range
8—79 years; mean 27.2 ± 15.8 years) and 24 males (age range
8—65 years; mean 32.2 ± 15.9years), with an overall age range of
8—79 years and mean age of 29.7 ± 16 years. Of note, one patient had
a previous history of McCune-Albright syndrome manifesting as poly-
ostotic fibrous dysplasia, one patient developed secondary ABC with
recurrent osteosarcoma, and one patient developed secondary ABC with
recurrent giant-cell tumor. There were no additional relevant patient
histories, metabolic disorders, or other significant medical co-morbid-
ities identified. Several of the pathology specimens consisted of cur-
ettage specimens, which histologically appeared as a mixture of pri-
mary tumor and discrete fragments of secondary ABC (Fig. 1).
Patients underwent various combinations of radiographic, CT, MR,
and/or nuclear medicine imaging prior to histologic diagnosis, as
L.B. Gutierrez, et al.
Fig. 4. 13-year-old female patient presented with a 6-month history of a rapidly
enlarging “bump” in her hand due to fibrous dysplasia with secondary ABC.
Frontal radiograph of the wrist (a) demonstrates a well-defined lytic and ex-
pansile lesion with mixed density centered at the fifth proximal metacarpal
diaphysis. Bone scan image of the bilateral hands (b) demonstrates significant
radiopharmaceutical uptake at the lesion site in the hand (arrowhead). Axial T2
weighted MR image through the metacarpals (c) demonstrates a well-defined
lesion centered in the fifth proximal metacarpal diaphysis, containing internal
septations and fluid-fluid levels (arrows).
detailed in Table 1; the table also lists every patient's gender, age, lesion
location, and lesion size. Lesions were discovered either due to imaging
for workup of pain (n = 35), unrelated trauma (n = 3), or an enlarging
mass (n = 6); five referral cases did not have the patients' presenting
clinical symptoms documented in our institution's electronic medical
record.
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Clinical Imaging 62 (2020) 23–32
The tumors associated with secondary ABCs, as well as the tumor
sizes, gender distributions, and patient ages associated with each type
of primary lesion are summarized in Table 2. Eleven primary bone le-
sions were associated with secondary ABC with the most frequent being
giant-cell tumor (Fig. 2), chondroblastoma (Fig. 3), fibrous dysplasia
(Fig. 4), osteoblastoma (Fig. 5), and osteosarcoma (Fig. 6). Interestingly
one case of secondary ABC was associated with osteonecrosis, a non-
neoplastic lesion. Cases occurred in ten anatomic locations as sum-
marized in Table 3, with the most frequent location being long bone
epiphyses.
Specific imaging characteristics for the six most frequent primary
bone lesions are summarized in Table 4. Specific imaging character-
istics for the five primary bone lesions with single case examples are
summarized in Table 5.
Linear regression analysis demonstrated that there was a significant
difference in age at diagnosis between lesion types (p = 0.004), in lesion
volume between lesion types (p = 0.003) (Fig. 7), and in lesion volume
between patient ages (p = 0.004) (Fig. 8). Chi-squared tests also de-
monstrated that there was a significant difference in lesion location
between lesion types (p = 0.001). These results are unsurprising as
several of the identified primary lesions have very well established
predilections for certain age groups and anatomic locations. For ex-
ample, chondroblastomas with secondary ABCs in our study occurred in
younger, less skeletally mature individuals, as well as in epiphyseal or
epiphyseal-equivalent locations, similar to previously reported cases of
primary chondroblastomas [3,4,7,9–11].
Chi squared testes demonstrated that there was a significant dif-
ference in the presence of a well-defined margin (p = 0.004), in the
presence of cortical thinning (p = 0.001), and in the presence of a soft
tissue mass between lesion types (p = 0.003), reflecting a difference in
lesion aggressiveness. In particular, none of the osteosarcoma cases had
well-defined margins, and all had associated soft tissue masses.
Chi squared tests demonstrated that there was a significant differ-
ence in the presence of internal architecture (p = 0.032) and in the pre-
sence of fluid-fluid levels between lesion types (p = 0.024). The cases of
Langerhans cell histiocytosis and osteonecrosis, as well as few of the
giant cell tumor and fibrous dysplasia cases, had no internal archi-
tecture. All of the osteoblastoma and osteosarcoma cases demonstrated
fluid-fluid levels, while the remaining primary lesion types variably
demonstrated them. Fluid-fluid levels have previously been reported in
16.2% of giant cell tumors, 16% of chondroblastomas, 18.8% of fibrous
dysplasias, 22.6% of conventional osteosarcomas, and 5% of chon-
dromyxoid fibromas [19,20]; although osteoblastomas have tradition-
ally been associated with fluid-fluid levels, only few case reports are
available in the literature [19,21]. All of the primary lesion types
containing fluid-fluid levels in our study demonstrated them at a higher
percentage than previously reported in the literature (Table 4). Of note,
the proportion of the fluid-fluid component relative to the primary bone
lesion component, although difficult to objectively quantify for each
lesion, greatly varied between each lesion by visual inspection, even
within the different histologic sub-groups. Some lesions only had few
scattered fluid-fluid levels (Fig. 1E), while others where almost com-
pletely replaced by fluid-fluid levels (Fig. 3B).
L.B. Gutierrez, et al.
Chi-squared tests demonstrated that there was no significant dif-
ference in gender distribution between lesion types (p = .405), in pre-
sence of margin sclerosis between lesion types (p = .113), in the presence
of an expansile lesion between lesion types (p = .098), in the presence of
a fracture between lesion types (p = .814), in the presence of periosteal
reaction between lesion types (p = .406), and in the presence of bone
marrow edema between lesion types (p = .147), implying that these
demographic and imaging characteristics are less helpful in distin-
guishing between the primary lesion types.
Except for cases of recurrent osteosarcoma, chondromyxoid fi-
broma, and osteonecrosis, most primary lesions evaluated with in-
travenous contrast demonstrated enhancement (30/32). Except for one
chondroblastoma case, all lesions that were evaluated with nuclear
medicine exams demonstrated radiopharmaceutical uptake (16/17).
Most lesions that were evaluated with MR imaging demonstrated pre-
dominant T1 isointensity and T2/proton density hyperintensity when
compared to muscle signal intensity; no lesion demonstrated pre-
dominant signal hypointensity on any sequence. One osteosarcoma case
did demonstrate T1 hyperintensity along with T2 hyperintensity, pos-
sibly reflective of blood products.
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Clinical Imaging 62 (2020) 23–32
Fig. 5. 24-year-old female patient presented with a
3-year history of ankle pain due to aggressive os-
teoblastoma with secondary ABC. Lateral ankle
radiograph (a) demonstrates a well-defined lytic,
expansile, exophytic lesion with soft tissue extension
and internal mineralization, centered at the ante-
rosuperior aspect of the talus. Axial contrast en-
hanced CT image of the left talus on bone window
(b) demonstrates a focus of internal nodular en-
hancement (asterisk), marginal irregularity, and
osseous erosion at the anterolateral aspect of the
lesion (arrowhead). Sagittal T1 weighted MR image
of the talus (c) demonstrates a well defined, and
exophytic talar lesion with predominant T1 iso-
intensity, as well as periosteal reaction (arrowheads)
and bone marrow edema. Sagittal short tau inversion
recovery (STIR) weighted MR image of the talus (d)
demonstrates a fluid-fluid level (arrow).
5. Discussion
Our study confirms that secondary ABCs are associated with a wide
variety of primary bone lesions, most frequently giant cell tumor,
chondroblastoma, fibrous dysplasia, and osteoblastoma, as well as
malignant tumors, such as osteosarcoma. One case of osteonecrosis, a
non-neoplastic lesion, was also associated with secondary ABC. The
imaging, anatomic, and clinical characteristics of each of the eleven
primary bone lesions associated with secondary ABCs in our study,
aside from the higher presence of fluid-fluid levels, were overall
equivalent to the expected findings of the primary bone lesions in-
dependent of secondary ABC, which is in concordance with previous
findings reported in the literature [2–5,7,9–11,15,21–53].
Our study also revealed that several of the imaging characteristics
were not helpful in differentiating one primary bone lesion from an-
other. For example, there was no significant difference in margin
sclerosis, presence of an expansile lesion, presence of a fracture, pre-
sence of periosteal reaction, or presence of bone marrow edema be-
tween lesion types. Also, most lesions demonstrated radio-
pharmaceutical uptake, enhancement, T1 isointensity, and T2
hyperintensity.
L.B. Gutierrez, et al.
Fig. 6. 20-year-old female patient presented with a 3-month history of knee
pain and swelling with associated 10-pound weight loss due to osteosarcoma
with secondary ABC. Frontal distal femur radiograph (a) demonstrates an ill-
defined lytic lesion with internal fluffy osteoid matrix and diffuse periosteal
reaction, centered at the distal femoral metaphysis and extending proximally
into the diaphysis. Frontal bone scan of the lower extremities (b) demonstrates
intense radiopharmaceutical uptake in the left distal femur, as well as proximal
skip lesions in the left femur (black arrows). Axial T2 weighted fat saturated MR
image of the distal femur (c) demonstrates fluid-fluid levels with thin septal
walls (white arrow). Axial contrast enhanced CT image of the distal femur (d)
demonstrates cortical breakthrough with associated soft tissue mass (arrow-
head), and internal dense osteoid matrix.
Interestingly, the giant cell tumor, chondroblastoma, fibrous dys-
plasia, osteoblastoma, osteosarcoma, and chondromyxoid fibroma cases
with secondary ABC demonstrated a higher percentage of lesions as-
sociated with fluid-fluid levels when compared to primary lesions
without secondary ABCs, supporting the idea that although fluid-fluid
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Clinical Imaging 62 (2020) 23–32
Table 3
Secondary ABC location summary.
Location Cases
Long bone, epiphysis 25 (51%)
Long bone, metaphysis 3 (6%)
Long bone, diaphysis 4 (8%)
Pelvis 4 (8%)
Tarsal 4 (8%)
Cranium 4 (8%)
Rib 2 (4%)
Mandible 1 (2%)
Spine 1 (2%)
Patella 1 (2%)
Total 49
levels are not pathognomonic for ABCs and can occur in several other
tumor entities, they can be more suggestive of their presence in the
appropriate clinical setting [13,54,55]. Still, in clinical practice, the
presence of a fluid-fluid level within a bone lesion by imaging does not
definitively establish the presence of a secondary bone cyst.
Our study is limited in that it is largely descriptive in nature and is
retrospective. Radiologic analyses of the 49 patient images were done
in consensus by two musculoskeletal radiologists with knowledge of the
lesion diagnoses, which introduces the possibility of observer bias.
Some primary lesion types in our study only had one or few case ex-
amples available, possibly weakening statistical power.
In conclusion, the cases of secondary ABC included in our study had
imaging, anatomic, and clinical features most consistent with the ex-
pected characteristics of their primary bone lesions independent of the
presence of a secondary ABC, with the most common primary lesions
associated with secondary ABC being giant cell tumor and chondro-
blastoma, located in the long bone epiphyses. Several of the primary
bone lesions containing secondary ABCs more frequently demonstrated
fluid-fluid levels than previously reported in the literature, however the
presence of a fluid-fluid level is not diagnostic of the presence of a
secondary bone cyst. Ultimately, the true value of radiologic correlation
in these cases is not to confirm the presence of a secondary ABC, but
rather to suggest the presence of the most likely primary bone lesion
based on lesion location, lesion imaging characteristics, and patient
demographics. This is particularly important in guiding tissue sampling
and appropriate treatment, as secondary ABCs are typically treated
based on the histology of the underlying primary bone lesion. Any
disparity in the expected clinical, imaging, and pathologic character-
istics identified in the workup of a bone tumor should raise suspicion of
a misdiagnosis, and necessitates further joint review of the findings by
the clinician, pathologist, and radiologist.
L.B. Gutierrez, et al. Clinical Imaging 62 (2020) 23–32

Table 4
Secondary ABC imaging characteristics (six lesions with multiple cases each).
Primary Lesion

Image characteristic GCT CB FD OB OS CF

Well-defined margin 16/17 (94%) 11/11 (100%) 5/6 (83%) 4/4 (100%) 0 2/2 (100%)
Margin sclerosis 2/17 (12%) 6/11 (55%) 1/6 (17%) 2/4 (50%) 1/4 (25%) 0
Expansile 17/17 (100%) 9/11 (82%) 5/6 (83%) 4/4 (100%) 4/4 (100%) 2/2 (100%)
Cortical thinning 17/17 (100%) 10/11 (91%) 6/6 (100%) 4/4 (100%) 2/3 (67%) 2/2 (100%)
Fracture 3/17 (18%) 0 0 0 0 0
Periosteal reaction 11/17 (65%) 9/11 (82%) 3/6 (50%) 3/4 (75%) 3/3 (100%) 2/2 (100%)
Bone marrow edema 8/13 (62%) 7/10 (70%) 1/4 (25%) 1/4 (25%) 3/3 (100%) 0
Internal architecture 15/17 (88%) 11/11 (100%) 4/6 (67%) 4/4 (100%) 3/3 (100%) 2/2 (100%)
Soft-tissue mass 3/17 (18%) 0 0 2/4 (50%) 3/3 (100%) 2/2 (100%)
Fluid-fluid level 4/13 (31%) 9/10 (90%) 2/4 (50%) 4/4 (100%) 3/3 (100%) 1/2 (50%)
Contrast enhancement 8/8 (100%) 6/6 (100%) 5/5 (100%) 4/4 (100%) 2/3 (67%) 2/2 (100%)
Radiopharmaceutical uptake 6/6 (100%) 2/3 (67%) 2/2 (100%) 1/1 (100%) 1/1 (100%) 1/1 (100%)
T1 signal hyperintensea 1/10 (10%) 2/9 (22%) 0 0 1/3 0
T1 signal isointensea 9/10 (90%) 7/9 (78%) 4/4 (100%) 4/4 (100%) 2/3 (63%) 1/1 (100%)
T2 signal hyperintensea 11/11 (100%) 8/8 (100%) 4/4 (100%) 2/4 (50%) 3/3 (100%) 2/2 (100%)
T2 signal isointensea 0 0 0 2/4 (50%) 0 0
PD signal hyperintensea 10/10 (100%) 6/6 (100%) 1/1 (100%) 1/1 (100%) n/a n/a
PD signal isointensea 0 0 0 0 n/a n/a

Note.—Ratio of cases with the listed imaging characteristic to the total cases analyzed for the imaging characteristics provided, as well as percentage. n/
a = Parameter not available for analysis.
GCT = Giant-cell tumor, CB = Chondroblastoma, FD = Fibrous dysplasia, OB = Osteoblastoma.
OS = Osteosarcoma, CF = Chondromyxoid fibroma, PD = Proton density.
a
Magnetic resonance signal intensity compared to muscle; no tumor had hypointense signal.

Table 5
Secondary ABC imaging characteristics (six lesions with single case each).
Primary Lesion

Image characteristic OF HA EH LCH ON

Well-defined margin + + + + −
Margin sclerosis + − n/a − −
Expansile + + + + −
Cortical thinning − + − + −
Fracture + − − − −
Periosteal reaction − + + − +
Bone marrow edema n/a + + n/a +
Internal architecture + + + − −
Soft-tissue mass − − − − −
Fluid-fluid level n/a − − n/a −
Contrast enhancement − + + n/a −
Radiopharmaceutical uptake n/a + n/a n/a +
T1 signal hyperintensea n/a − − n/a −
T1 signal isointensea n/a + + n/a + Fig. 7. Bar graph demonstrating differences in lesion volume by primary lesion
T2 signal hyperintensea n/a − + n/a + type.
T2 signal isointensea n/a + − n/a −
PD signal hyperintensea n/a − n/a n/a n/a
PD signal isointensea n/a + n/a n/a n/a

Note.— n/a = Parameter not available for analysis, + = Present, − = Absent.

OF = Ossifying fibroma, HA = Hemangioma, EH = Epithelioid hemangioma.
LCH = Langerhans cell histiocytosis, ON = Osteonecrosis, PD = Proton den-
sity.
a
Magnetic resonance signal intensity compared to muscle; no tumor had
hypointense signal.

Funding

This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

None.
Fig. 8. Linear regression analysis, demonstrating differences in lesion volume
by patient age at diagnosis.

31
L.B. Gutierrez, et al.
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