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724

Posttreatment Imaging of Pediatric

Musculoskeletal Tumors1
Andrew M. Zbojniewicz, MD
Joel I. Sorger, MD
Abbreviation: FDG = 2-[fluorine 18]
fluoro-2-deoxy-d-glucose
RadioGraphics 2014; 34:724–740
Published online 10.1148/rg.342135069
Content Codes:
1
From the Division of Pediatric Radiology
(A.M.Z.) and Department of Orthopedic Sur-
gery (J.I.S.), Cincinnati Children’s Hospital
Medical Center, 3333 Burnet Ave, MLC 5031,
Cincinnati, OH 45229. Recipient of a Certifi-
cate of Merit award for an education exhibit at
the 2012 RSNA Annual Meeting. Received
April 19, 2013; revision requested May 24 and
received July 24; accepted July 26. The authors
have no financial relationships to disclose. Ad-
dress correspondence to A.M.Z. (e-mail:
Andrew.zbojniewicz@cchmc.org).
Pediatric patients who are diagnosed with musculoskeletal tumors
often require serial imaging both during and after treatment. Al-
though many of the treatments used in adults overlap with those
used in children and adolescents, the growing skeleton presents
specific challenges that require a unique approach. Surgical treat-
ment of benign osseous lesions typically requires only curettage and
bone grafting, whereas that of osseous malignancies generally con-
sists of wide excision and limb salvage, with either endoprosthetic
or biologic reconstruction. Current conventional endoprostheses
consist of modular components that allow intraoperative custom-
ization; however, if there is great potential for future growth, an
expandable endoprosthesis may be required. Biologic reconstruc-
tion may consist of an allograft and/or autograft and, in some cir-
cumstances, can spare the growth plates in a child, thereby allowing
normal growth. Expected posttreatment imaging findings in soft-
tissue tumors may include muscle flaps and postoperative fluid col-
lections. Medical treatment, including radiation therapy and che-
motherapy, can have predictable imaging manifestations, including
signal alterations in bone marrow, muscle, and subcutaneous fat.
Finally, treatment complications may manifest with clinical symp-
toms and include infection or mechanical failure, although other
complications such as local tumor recurrence may go clinically un-
detected until surveillance imaging. Familiarity with the expected
posttreatment imaging findings in pediatric patients with musculo-
skeletal tumors can aid in the detection of complications.
©
RSNA, 2014 • radiographics.rsna.org

Introduction
Although diagnostic radiology training largely consists of learning to
make the correct diagnosis at initial presentation, patients diagnosed
with musculoskeletal tumors frequently require follow-up imaging,
often with multiple modalities, and consequently represent a sub-
stantial portion of the examinations performed in a radiology depart-
ment. In addition, given the improvement in survival rates for many
sarcomas, many patients who were initially diagnosed as children
continue to be followed up into adulthood. These patients often have
altered anatomy or postsurgical hardware, and interpretation can be
intimidating if a solid foundation regarding the appropriate terminol-
ogy and expected posttreatment findings has not been laid.
In this article, we discuss the expected posttreatment changes
and complications associated with the different types of surgical and
medical treatment for both benign and malignant osseous lesions
and soft-tissue tumors.
RG • Volume 34 Number 3
Figure 1. Postoperative radiograph obtained in a
12-year-old boy who had undergone curettage, bone
grafting, and internal fixation for a recurrent aneurysmal
bone cyst approximately 6 weeks earlier shows packing
of the cavity with allograft chips centrally (arrow) and
with a more homogeneously dense bone graft substitute
at the upper and lower margins (arrowheads).
Expected Posttreatment Changes
Surgical Treatment
of Benign Osseous Lesions
Surgical treatment of benign osseous lesions of-
ten consists of curettage and filling of the cavity
with either cement (polymethylmethacrylate) or
bone graft material. Although cement does not
provide biologic reconstruction, it is often used
in adults, particularly in giant cell tumors, due to
(a) its potential to destroy tumor cells by means
of thermonecrosis of the remaining tumor cells in
the capsular lining of the tumor, and (b) its abil-
ity to provide immediate structural support (1,2).
However, cement can also cause thermal damage
to articular cartilage and increased stiffness of
subchondral bone, which can lead to early osteo-
arthritis and the need for joint replacement (1).
Cement is typically not used in children ow-
ing to its potential to affect skeletal growth; as a
result, bone grafting is generally the treatment of
choice in these patients (2). Bone graft materials
include autografts, allografts, and synthetic bone
graft substitutes. The goal of treatment in benign
bone tumors is removal of the tumor followed
by the reestablishment of bone morphology and
structural support without compromising axial
growth, joint function, or overall morbidity (2).
Occasionally, internal fixation—often with plates,
screws, or (when the growth plates are closed)
intramedullary nails—is used in conjunction with
bone grafting if the lesion is large and the bone
is structurally compromised (Fig 1) (3). Larger
Zbojniewicz and Sorger 725
bone defects can also be supported with use of
onlay or strut grafts, usually allografts.
Bone graft materials provide a scaffold for new
bone formation and healing and can also serve as
a substrate for direct delivery of antibiotics (4).
Osseous incorporation of the graft material re-
quires structural incorporation by means of new
bone formation as well as adaptive remodeling
of the graft material in response to mechanical
stress (4).
New bone formation occurs by means of os-
teogenesis, osteoinduction, or osteoconduction.
To invoke osteogenesis, a graft must contain
osteogenic precursor cells capable of new bone
formation (4). The term osteoinduction refers to
recruitment of pluripotential mesenchymal cells
that can differentiate into osteoblasts (4). Os-
teoconduction works primarily by providing a
framework for ingrowth of vessels and migration
of host cells capable of osteogenesis (4). Creeping
substitution is a process of remodeling in which
graft resorption occurs in conjunction with new
bone formation (4). Different graft materials can
be combined to take advantage of their different
strengths.
Autografts are often preferred; however,
quantities are limited—particularly for large,
multicentric, or polyostotic lesions or in small
children—and harvesting is associated with donor
site morbidity (2,3,5). An autograft can produce
bone by means of osteogenesis, osteoinduction,
or osteoconduction and usually consists of corti-
cal, cancellous, or corticocancellous bone.
Time to complete incorporation of an auto-
graft (also known as healing or consolidation)
depends on the type of graft used (eg, cancellous
versus cortical bone) and, in the case of cancel-
lous or corticocancellous bone, the size of the
defect. There is scant literature on the expected
time to healing of an autograft in the setting of
bone lesion curettage. Glancy et al (5), evaluating
differences in the use of autografts and allografts
for the filling of benign bone lesions in children,
found that healing can take several months for
smaller lesions (<60 mL), although in cases in-
volving a combination of large (>60-mL) and
small lesions, the mean time to healing of an au-
tograft was 21 months. In clinical practice, how-
ever, much like patients with fractures, patients
who have undergone curettage and grafting are
treated with 3–4 months of non–weight bearing.
Afterward, follow-up radiographs are obtained to
evaluate for the presence of incorporation. Com-
plete incorporation need not be present before
increased patient activity is allowed.
At computed tomography (CT), an autograft
is typically isoattenuating relative to adjacent cor-
tical bone; however, its appearance at magnetic
726 May-June 2014
resonance (MR) imaging can be variable (4).
With cancellous bone autografts, graft necrosis
and ingrowth of granulation tissue during the ini-
tial period of incorporation will manifest as hy-
pointense T1 signal and iso- to hyperintense T2
signal (4). At the time of complete incorporation,
the signal should more closely resemble that of
normal yellow bone marrow, including the pres-
ence of hyperintense T1 signal similar to that of
adjacent bone (4).
Allografts support new bone formation pri-
marily through an osteoconductive mechanism
and can take a variety of forms, including chips,
morsels, paste, or segments. The rate of allograft
incorporation depends on many factors, includ-
ing particle size, whether bone was freeze dried
or frozen, and the size of the defect to be filled
(5,6). Glancy et al (5) found slightly longer heal-
ing times for allografts than for autografts. Al-
though small (<60-mL) lesions took an average
of 6 months to heal with an allograft, the mean
time to healing for a combination of large (>60-
mL) and small lesions was 27 months. Similar
success rates were seen with small lesions filled
with either an autograft or an allograft; however,
large solitary lesions healed faster and more com-
pletely with an autograft (5). In a more recent
study that made use of a microparticulate cortical
allograft, Temple and Malinin (7) found a wide
variability in time to healing, with partial incor-
poration occurring between 4 and 68 weeks and
complete incorporation occurring between 6 and
108 weeks. The authors did not comment on the
relationship between the rate of healing and the
size of the lesion (7).
At radiography and CT, the density (attenua-
tion) of an allograft resembles that of normal cor-
tical bone (Fig 1) (4). Soon after allograft place-
ment, fibrovascular granulation tissue is present
around the graft, accounting for a definable
boundary between host bone and the allograft
(4). It is at this interface that osteoclastic activity
and bone resorption occur, which together with
osteogenesis related to vascular and osteogenic
precursor cell invasion result in graft incorpora-
tion (4). This discrete boundary disappears as a
result of trabecular ingrowth during incorpora-
tion (4).
Because of the lack of viable marrow elements,
the MR imaging appearance of an allograft has
been described as consisting of decreased T1 and
T2 signal until incorporation occurs, after which
a pattern similar to that of normal marrow is seen
(4). However, Jelinek et al (8) investigated the
MR imaging appearance of chip allografts after
bone tumor curettage and found a pattern of de-
creased T1 and T2 signal in only four of 18 cases
(22%). Instead, they frequently found speckled
radiographics.rsna.org
areas of hyperintense T2 signal mixed with small
areas of hypointense T1 and T2 signal as well as
occasional areas of hyperintense T1 signal, even
when surgery had been performed within the
past 4 months. They attributed the hyperintense
T2 signal to necrotic marrow elements seen at
histologic analysis. Similarly, they were inclined
to believe that the hyperintense areas of T1 sig-
nal were associated with intact fat cells and the
hypointense areas of T1 and T2 signal with bone
trabeculae (8).
Another type of allograft known as demin-
eralized bone matrix consists of allograft bone
that has undergone an acid extraction process
to remove the inorganic minerals, with subse-
quent production of a composite that includes
noncollagenous proteins, bone growth factors,
and collagen that can contribute to bone pro-
duction through osteoinduction (4). The disad-
vantages of demineralized bone matrix are that
the structural rigidity has been removed from
the material and that the material is radiolucent.
However, demineralized bone matrix can be
combined with a cancellous bone allograft or
ceramic material, which can provide osteocon-
ductive properties.
Ceramic material is a common type of bone
graft substitute that is encountered following
tumor curettage in children and adolescents. It
is a homogeneous, radiographically dense mate-
rial composed of calcium sulfate, calcium phos-
phate, hydroxyapatite, tricalcium phosphate, or
a combination thereof and may take the form
of pellets, paste, or cement (4). Ceramic mate-
rial forms bone by means of an osteoconductive
framework used for osseous ingrowth-osteogen-
esis. Creeping substitution with bone resorption
can be a normal part of incorporation of this
graft material (2,4). Bone resorption occurs
more readily with calcium sulfate than with hy-
droxyapatite (2).
Ceramic material appears denser than adjacent
native bone, and a thin, well-defined radiolucent
zone at the host-graft junction is an expected
finding early after placement, but this radiolu-
cent zone should disappear as osseous ingrowth
occurs (Fig 2) (2,4). In two studies in which ce-
ramic bone graft substitutes were used, the mean
time for this disappearance was about 4 months
(2,9). The radiodense ceramic material itself can
resorb over time. One study showed substantial
resorption of the ceramic material in conjunction
with osseous ingrowth over a period of several
years in many patients; however, complete re-
sorption was never observed (3). There were also
cases that demonstrated osseous ingrowth but no
resorption of the ceramic material itself even after
15 years of follow-up (3).
RG • Volume 34 Number 3
Surgical Treatment
of Osseous Malignancies
Surgical treatment options for osseous malignan-
cies include amputation, rotationplasty, and limb
salvage. In the 1970s, amputation was the main
form of surgical treatment; however, with ad-
vances in surgical technique, imaging, and medi-
cal therapy, limb salvage is now the standard of
treatment in bone sarcomas (85%–90% of cases)
(10–12). The goal of limb salvage surgery is to
preserve the limb with adequate function without
sacrificing overall survival (10).
An additional consideration in choosing a
treatment option in the growing child is the po-
tential for development of a leg length discrep-
ancy if growth plate resection is required during
the course of treatment. In general, if bone age
and growth charts predict a leg length discrep-
ancy of less than 30 mm, the affected limb can be
prophylactically lengthened by 10–20 mm at the
time of surgery, ultimately resulting in an accept-
able leg length discrepancy following cessation of
growth (10). However, if a leg length discrepancy
of more than 30 mm is predicted, this discrep-
ancy must be addressed surgically (7).
Rotationplasty can be performed following
distal femoral or proximal tibial resection and
consists of ankle rotation and use of the ankle as
a knee joint, ultimately treating the patient as if
he or she had undergone below-the-knee amputa-
tion with fitting of a prosthesis. Rotationplasty has
been reported to yield good to excellent results;
however, the primary disadvantage is thought to
be both cosmetic and the potential psychologic
implications of the procedure (13).
Zbojniewicz and Sorger 727
Figure 2. Expected posttreatment
findings in a 10-year-old boy with
a history of several prior fractures
through a unicameral bone cyst. The
patient underwent placement of a
bone graft substitute. (a) Radiograph
obtained 2 months after surgery
shows the expected thin radiolucent
zone (arrows) around the graft mate-
rial. (b) On a radiograph obtained
over 2 years after surgery, there is
excellent incorporation with partial
resorption of graft material and re-
placement by host bone (arrow).
Two broad categories of reconstruction exist:
endoprosthetic and biologic reconstruction. En-
doprosthetic reconstruction generally consists of
either a conventional endoprosthesis or an expand-
able (ie, extensible) endoprosthesis. Traditionally,
conventional endoprostheses were custom made
due to the relatively small demand. Over time,
however, the indications for these implants grew
to include metastatic disease, comminuted peri-
articular fractures, and revision arthroplasty (14).
To provide for these new indications, modular
implants were developed that allow intraoperative
customization of osseous resection lengths (Figs
3, 4) (14). The intramedullary stems at the femur
and tibia in these modular implants can be fixated
with cement or with porous ingrowth stems, which
have become available more recently (14).
Although the most common type of knee ar-
throplasty is an unconstrained arthroplasty (ie,
there is no connection between the femoral and
tibial sides), functioning ligaments and muscles
are needed to maintain stability about the knee
when this type of prosthesis is used. Tumor sur-
gery often requires the resection of knee ligaments,
resulting in a poor soft-tissue envelope, which
destabilizes the joint and necessitates the use of
constrained arthroplasty (14,15). The initial design
used a fixed hinge, a type of constrained prosthesis
that allowed flexion and extension but not rota-
tion (16). However, newer designs make use of a
rotating hinge mechanism, which decreases the
torsional stresses that can lead to loosening (16).
Expandable endoprostheses are extended in
length, usually either by means of (a) a minimally
invasive technique that consists of a worm screw
728 May-June 2014
Figures 3, 4. (3) Modular endoprostheses. Photograph
shows a tibial stem with cement around its proximal
aspect (arrows), a distal femoral rotating hinge compo-
nent with attached modules 80 and 90 mm in length
(center), and a single longer module measuring 160 mm
(right). In the rotating hinge component, the metal post
attached to the hinge slides into the tibial component on
the left, thereby allowing rotation. Modules are avail-
able in multiple sizes for intraoperative customization.
(4) Modular endoprosthesis in a 16-year-old boy. Radio-
graph shows a distal femoral rotating hinge component
(green bracket) with two modules (white brackets) and
a modular femoral stem (yellow bracket).
mechanism and requires general anesthesia and
an open procedure, or (b) a noninvasive tech-
nique, in which lengthening is achieved by plac-
ing the device in an external electromagnetic field
(Fig 5) (10). Lengthening is limited to 10 mm at
a time due to the risk of fixed flexion deformity
or neurapraxia associated with greater lengthen-
ing (10). These implants eventually require revi-
sion to a conventional endoprosthesis after the
patient has stopped growing.
Biologic reconstruction most commonly con-
sists of either an intercalary (ie, interpositional) or
osteoarticular allograft, both of which are typically
fixated with plates, screws, or (in skeletally mature
patients) intramedullary nails (Figs 6, 7). At the
time of harvest, these allografts are stripped of all
soft tissues except important ligaments and ten-
dinous insertions. Vascularized fibular autografts
can also be used for reconstruction, often in con-
junction with an allograft (Fig 8). Less commonly,
an allograft-prosthesis composite can be used for
reconstruction. Ilizarov segmental bone transport
has also been used to fill massive bone defects fol-
lowing tumor resection (17,18).
radiographics.rsna.org
Figure 5. Expandable endoprosthesis in a 10-year-old
girl. (a) Lateral radiograph shows an expandable en-
doprosthesis. Lengthening of the prosthesis is achieved
with an electromagnetic field, which causes the spring
(arrow) to decompress and lengthen. (b) Photograph
shows the implant ex vivo.
Uncomplicated osteoarticular and intercalary
allografts appear denser than host bone following
surgery, often with a gradual decrease in density
over the course of 2 years (16). Two studies of
the radiographic appearance of osteoarticular and
intercalary allografts showed a gradual increase
in callus formation at the host-allograft junction
that peaked at 21 months and 9 months, respec-
tively (19,20). Mean time to union in the uncom-
plicated intercalary allografts and in the majority
of osteoarticular grafts was about 1 year and
9–11 months, respectively, although a distinction
between complicated and uncomplicated cases
was not made in the second study (19,20).
The MR imaging appearance of osteoarticu-
lar allografts was described by Kattapuram et
al (21) as consisting of persistent fatty marrow
signal, but with scattered heterogeneous areas
of decreased T1 and increased T2 signal in the
marrow that was thought to represent saponified
fat or necrotic marrow. In addition, the authors
found that endosteal and periosteal enhancement
occurred from several months to 2 years after
surgery, which they believed might be related to
RG • Volume 34 Number 3 Zbojniewicz and Sorger 729

Figures 6–8. (6) Intercalary allograft in a 20-year-old man with a history of mesenchymal
chondrosarcoma. Radiograph shows an intercalary allograft fixated with a medial plate and
screws. Arrowheads = proximal and distal host-allograft junctions. (7) Osteoarticular allograft
in a 24-year-old woman with a history of osteosarcoma of the proximal humerus. Radiograph
shows an osteoarticular allograft consisting of the proximal and middle humerus with a single
host-allograft junction (arrow) fixated with a plate and associated screws. (8) Fibular autograft
and allograft in an 8-year-old girl with a history of osteofibrous dysplasia–like adamantinoma.
Radiograph of the right lower leg shows reconstruction consisting of a fibular autograft and a
fibular allograft in tandem, which were used in an intercalary fashion and fixated with a me-
dial plate and associated screws. The growth plates at the proximal and distal tibia were spared
(arrows). Subsequent studies showed normal growth at these sites.

vascular ingrowth as well as potentially to new
appositional bone laid down to bind the soft tis-
sues to the cortex (21).
Surgical Treatment
of Soft-Tissue Tumors
Expected posttreatment change following surgical
treatment of soft-tissue tumors generally consists
of either a postoperative fluid collection or changes
that reflect reconstructive surgery (eg, flaps).
Postoperative fluid collections usually consist
of seromas or hematomas. Seromas are well de-
fined and display homogeneously hyperintense
T2 signal with thin peripheral enhancement at
MR imaging after the administration of contrast
material (22). In general, seromas resolve within
3–18 months, although they can persist for much
longer (22). Hematomas can vary in their MR
imaging appearance depending on their age and
can range from hypo- or isointense relative to
muscle at T1-weighted imaging and hypointense
at T2-weighted imaging in the acute stage (<1
week), to homogeneously or heterogeneously
hyperintense at T1- and T2-weighted imaging in
the subacute (1 week–3 months) and chronic (>3
months) stages (23). Subacute and chronic he-
matomas often have a hypointense peripheral rim
at T2-weighted and gradient-echo imaging due to
the presence of hemosiderin-laden tissue, which
may increase in extent with age of the hemotoma
(23,24). Rarely, chronic hematomas can have foci
of nodular enhancement that require biopsy to
differentiate them from tumor (22).
Because of the wide excision required for
treatment of a soft-tissue malignancy, a large
soft-tissue defect may need to be covered with
the aid of a flap. Flaps can be cutaneous, fascio-
cutaneous, musculocutaneous, or osteocutane-
ous, or they can consist of pure muscle, which
may require an additional skin graft. In broad
terms, a flap is either free, requiring reanastomo-
sis of the vascular supply, or pedicled, in which
the vascular supply is left intact. Musculocutane-
ous or muscle flaps normally display a muscle
edema pattern, sometimes with postcontrast
enhancement, particularly if there has been ir-
radiation of the region (Fig 9) (22). An expected
finding of progressively decreasing muscle bulk
and increasing fatty infiltration occurs over time,
with the muscle edema pattern and enhancement
resolving in one-third of patients within 24 and
18 months, respectively (22).
730 May-June 2014 radiographics.rsna.org

Figure 9. Rotational gastrocnemius muscle flap in a 21-year-old man with a history of

synovial sarcoma resection who required coverage of a large soft-tissue defect. (a) Axial fat-
suppressed T2-weighted MR image obtained 10 days after surgery shows a typical muscle
edema pattern (arrows). (b) Coronal T1-weighted MR image shows the normal muscle tex-
ture of the flap, which overlies a defect in the patella.

Medical Treatment increase in size; therefore, an increase in size does

Medical treatment includes radiation therapy
and chemotherapy. Choosing a radiation therapy
portal for treatment of a soft-tissue tumor can be
complicated in children due to the potential for
disturbance of growth. The epiphysis is the most
radiosensitive part of the skeleton, and permanent
growth retardation can occur with doses greater
than 1200 cGy (25). A higher risk of growth dis-
turbance is seen in bones that contribute greater to
length (eg, long bones), in younger patients, and
with increased radiation doses (25).
It is important to remember that all of the ex-
pected changes attributed to radiation therapy
must be confined to the radiation portal. Evidence
of the location of the radiation portal is often dis-
tinctly seen with multiple imaging modalities (Fig
10), but it may also be found upon reviewing the
electronic medical record.
Complete replacement of normal marrow by fat
is a common finding and generally occurs within
6–8 weeks following completion of treatment (22).
Regeneration of normal marrow may occur over
time in young patients, but fatty replacement can
be permanent (22).
More focal marrow signal abnormalities, some-
times referred to as radiation osteitis, have also
been described in long bones following radiation
therapy or chemotherapy in patients with soft-
tissue sarcomas (22,26). These changes are gen-
erally seen following a mean dose of about 6000
cGy and often manifest in a delayed fashion, with
initial recognition taking place between 1 and 49
months after completion of treatment (22,26). It is
important to note that these foci can fluctuate or
not necessarily imply metastatic disease (26).
At MR imaging, radiation osteitis consists of
linear-curvilinear, patchy, or mixed foci of signal
change with all sequences (22,26). These foci
typically follow signal patterns similar to those of
red marrow, demonstrating signal between that of
muscle and fat on T1-weighted images, signal be-
tween that of muscle and fluid on fat-suppressed
T2-weighted or short inversion time inversion-
recovery images, and heterogeneous enhancement
(26). Although these changes can resemble os-
teonecrosis, they may actually represent localized
gelatinous (serous) transformation, as can be seen
in patients with acquired immunodeficiency syn-
drome, starvation, cachexia, or anorexia nervosa,
among other disorders (26).
An abnormal reticular or lattice-like pattern
of increased signal within subcutaneous fat and a
more diffuse muscle edema pattern is often seen
on fat-suppressed T2-weighted or short inversion
time inversion-recovery images obtained following
radiation therapy, gradually increasing in conspi-
cuity for the next 12–18 months (22). Thereafter,
the appearance may return to normal over a 2–3-
year period in approximately 50% of patients (22).
In adults, a rare radiation-induced pseudotu-
mor also known as inflammatory pseudotumor has
been described, which consists of varying amounts
of fibrosis and vascular ectasia at histopathologic
analysis and can mimic local tumor recurrence
(27). To our knowledge, this entity has not been
reported in pediatric patients, perhaps due to the
rarity of the process or the long time interval be-
tween radiation therapy and development of the
RG • Volume 34 Number 3
Figure 10. Muscle edema pattern in a 20-year-
old girl with synovial sarcoma who had under-
gone resection and radiation therapy (completed
approximately 4 months earlier). Sagittal fat-sup-
pressed T2-weighted MR image shows a muscle
edema pattern with distinct borders (arrows) that
correspond to the radiation portal.
pseudotumor. However, as more patients who
were originally diagnosed as children or young
adults continue to be followed up at pediatric cen-
ters, conditions that previously have been recog-
nized only in adults may become relevant.
On average, radiation-induced pseudotumor
manifests 38 months following treatment, and it
typically consists of a focal area of increased T2
signal with corresponding postcontrast enhance-
ment (27). Although there are no known definitive
imaging criteria for differentiating a pseudotumor
from recurrent tumor, ill-defined margins and lack
of early enhancement within 1–2 minutes at dy-
namic contrast-enhanced subtraction imaging can
suggest the presence of a pseudotumor (27,28).
Complications
Surgical Treatment
of Benign Osseous Lesions
Complications of the treatment of benign bone
lesions can include fracture, tumor recurrence,
graft resorption, and infection, as well as chronic
pain, scarring, or local sensory loss at the donor
site in autografts and potential for disease trans-
mission or mild rejection in allografts (4).
Persistent or developing radiolucency—often
at the margins of the graft—following graft place-
ment may indicate tumor recurrence or graft
resorption without incorporation (Fig 11). Cross-
sectional imaging can aid in diagnosing tumor
Zbojniewicz and Sorger 731
recurrence. In two cases of tumor recurrence fol-
lowing allograft placement, Jelinek et al (8) found
that the presence of homogeneous decreased T1
signal and intermediate T2 signal at the margins
of the graft material was indicative of tumor re-
currence, rather than the expected speckled pat-
tern seen with normal allografts. The continued
presence over time of the radiolucent band at the
host-graft junction suggests lack of graft incorpo-
ration. At cross-sectional imaging, the absence of
normal marrow signal at MR imaging or lack of
trabecular bone at CT over time can be seen with
ingrowth of fibrous tissue and lack of incorpora-
tion in allografts (4).
Fracture of the graft may occur in the setting
of an onlay or strut graft used for support of large
bone defects. Devascularization of a segmental
fibular autograft can also occur, resulting in graft
failure, and is heralded by loss of normal marrow
signal on T1- and T2-weighted images (4).
Surgical Treatment
of Osseous Malignancies
Several complications can be seen with endopros-
thetic reconstruction, including infection, mechan-
ical failure, and local disease recurrence (10,29).
Mechanical failure is a general term and can in-
clude aseptic loosening, implant failure, instability,
periprosthetic fracture, pain, and stiffness (29).
Deep infection is defined as clinical evidence
of infection with positive cultures or peripros-
thetic pus and histologic evidence of infection at
the time of surgery (30). The best outcomes for
patients undergoing treatment for deep infection
are seen with a two-stage revision, which includes
removal of the prosthesis, placement of an anti-
biotic-impregnated spacer for a minimum of 6
weeks, intravenous administration of antibiotics,
and subsequent placement of a new prosthesis
after the infection has cleared (Fig 12) (30). Un-
fortunately, even with this treatment, the success
rate is only 72%, and amputation may still be
required (30). However, in one study evaluating
the long-term survival of patients who had under-
gone endoprosthetic reconstruction, two patients
with chronic infections who refused surgical re-
vision continued to live for more than 10 years
with minimal complications (29).
Clinical concern for aseptic loosening is raised
when a patient complains of thigh or leg pain that
occurs with weight bearing but is relieved by rest,
whereas with infection there is often constant pain.
An additional sign that raises suspicion for aseptic
loosening is start-up pain (ie, pain experienced
with the first couple of steps after beginning to
walk). However, it should also be noted that pa-
tients with infection or aseptic loosening can be
asymptomatic (31).
732 May-June 2014 radiographics.rsna.org

Figure 11. Tumor recurrence in an 11-year-old boy. (a) Intraoperative

fluoroscopic image obtained at the time of initial biopsy shows an expansile
lytic lesion at the proximal tibial metadiaphysis. (b) Radiograph obtained
3 months later following curettage and bone grafting shows cancellous al-
lograft bone (dense material filling the lytic lesion). (c) Radiograph obtained
9 months after the initial bone grafting procedure shows the development of
widespread radiolucency and increased expansion, findings that are indica-
tive of recurrence. (d) Axial fat-suppressed T2-weighted MR image confirms
a recurrent aneurysmal bone cyst with multiple fluid levels.

Figure 12. Antibiotic-im-

pregnated spacer in a 15-year-
old girl with an infected osteo-
articular allograft. (a) Scout
image from a CT scan shows
an antibiotic-impregnated ce-
ment spacer (arrows) fixated
with a K wire. (b) Radiograph
shows a new endoprosthesis
that was placed after clearance
of the infection.
RG • Volume 34 Number 3 Zbojniewicz and Sorger 733

Figure 13. Aseptic loosening of a prosthesis in a 10-year-old girl. (a) Radiograph shows an expand-
able endoprosthesis with cement around the tibial stem (white arrows). Note the spring mechanism
that allows for lengthening of the prosthesis (black arrows). (b) Radiograph obtained 14 months
later shows interval development of a well-defined radiolucency surrounding the tibial stem and
proximal tibial component (white arrows) as well as buttressing of the posterior cortex (arrowhead).
Note the slight interval lengthening of the endoprosthesis (black arrows). (c) Radiograph obtained
more than 3 years after initial surgery shows a continued increase in the size of the radiolucency (white
arrows), with tilting of the stem and so-called windshield wipering, findings that are indicative of defi-
nite loosening. Further lengthening of the endoprosthesis (black arrows) is also noted.

To our knowledge, there have been no studies
investigating the role of imaging in the evalua-
tion of oncologic endoprosthetic loosening in the
setting of limb salvage. Given that the prostheses
used in oncologic reconstruction at the knee re-
quire the use of an intramedullary stem at the fem-
oral and tibial sides, imaging findings described in
association with nononcologic hip prostheses are
thought to be the most relevant, and some clues as
to what to look for can be gleaned from this litera-
ture. It should be noted that criteria for loosening
cannot reliably help distinguish between aseptic
and septic loosening due to frequent overlap in
their imaging appearances.
According to radiographic criteria for evaluat-
ing hip arthroplasties performed with cement, a
thin radiolucent zone less than 2 mm in width at
both the component-cement and bone-cement
interfaces may be normal if there is no progres-
sion after 2 years (32). Similarly, in noncemented
components, a well-defined radiolucency around
the stem measuring less than 2 mm, often with
an associated thin sclerotic margin, is also con-
sidered normal as long as there is no progression
after 2 years (31,32).
The thin radiolucent zone at the component-
cement interface may be due to minimal motion
during cement setting, incomplete contact be-
tween the cement and stem at the time of surgery,
or Mach effect (the visual perception of edge en-
hancement at the boundary between the cement
and component where there is an abrupt change
in the degree of luminance that may produce an
artifactual linear radiolucency) (31,32). A thin ra-
diolucent band with a well-defined sclerotic mar-
gin at the cement-bone interface may represent
a thin fibrous membrane produced by a reaction
of bone with cement, which as mentioned earlier
will normally stabilize by 2 years following surgery
(31). In the noncemented prosthesis, a thin radio-
lucency at the component-bone interface may be
related to fibrous ingrowth or micromotion result-
ing from differences in stiffness between the pros-
thesis and adjacent bone (31).
Probable loosening in the setting of a cemented
component is suggested by a radiolucent zone
greater than 2 mm, whereas definite loosening
is characterized by a progressive increase in the
size of a radiolucent zone, component migration,
change in alignment, or cement fracture (Fig 13)
(32). The appearance of noncemented components
can vary more widely, with the presence of mild
cortical thickening, endosteal sclerosis, or periosteal
reaction still being considered acceptable and not
734 May-June 2014 radiographics.rsna.org

Figure 14. Infected endoprosthesis in a 10-year-old girl. (a) Radio-

graph obtained approximately 1 month after placement of an expandable
endoprosthesis shows the endoprosthesis with cement around the tibial
stem. (b) Coronal 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) PET
image obtained 5 months later shows mildly increased uptake around
the medial tibial stem (arrow). (c) Radiograph obtained 8 months after
a shows development of an ill-defined radiolucency around the stem
(arrows). (d) Corresponding coronal FDG PET image shows increased
uptake on both sides of the stem (arrows). (e) Radiograph obtained 2
months after c shows interval growth of the ill-defined radiolucencies,
which are now more focal in appearance (white arrow), as well as devel-
opment of periosteal reaction (black arrows).

necessarily indicative of loosening (32). However,

extensive cortical thickening, extensive endosteal
sclerosis, or a radiolucent zone greater than 2 mm
all indicate probable loosening, whereas definite
loosening is present when a progressively larger
shift in position is seen, as evidenced by compo-
nent migration or tilt (32).
Histopathologic analysis reveals that the radio-
lucent zone in the setting of aseptic loosening of a
cemented component represents a layer of active
connective tissue containing (a) synovium-like
cells near the cement; (b) fibrovascular tis-
sue, foreign body giant cells, polyethylene, and
polymethylmethacrylate debris in the middle; and
(c) interlocking fibrous tissue near the cancellous
bone (31). A similar process occurs with aseptic
loosening of noncemented components (31).
Serial radiographs showing progressive,
well-defined round areas of radiolucency at the
cement-bone or component-bone interface are
suggestive of infection or particle disease (also
known as granulomatous disease, granulomatous
pseudotumor, or cement disease) (31). Particle
disease can occur with cemented or noncemented
components and is due to metal, cement, or
primarily polyethylene fragments that induce a
localized inflammatory reaction, resulting in os-
teolysis (31). However, small, well-defined round
areas of radiolucency that manifest immediately
following surgery and are stable over time at
the cement-bone interface or within the cement
mantle may simply be related to air bubbles in-
troduced at the time of surgery (31).
Criteria for loosening after revision are even
more difficult to interpret, since deep radiolucent
zones related to prior loosening may be seen. The
presence of progressively changing radiolucent
zones or component migration is the key to the
diagnosis of loosening following revision (32).
RG • Volume 34 Number 3
Accurate differentiation between aseptic and
septic loosening in the setting of hip and knee
arthroplasty is often not possible due to overlap
in their radiographic appearances. Consequently,
the use of other modalities for this purpose has
been explored. The literature on nononcologic
arthroplasties is helpful in evaluating the useful-
ness of other imaging modalities in differentiating
infection from aseptic loosening in patients with
oncologic implants.
Bone scintigraphy can be useful in that a nega-
tive study effectively excludes a prosthetic com-
plication (33). However, a positive study is less
useful, and, although focal uptake at the stem of a
cemented arthroplasty after 1 year is suggestive of
aseptic loosening, uptake around porous coated
prostheses can be a normal finding for consider-
ably longer than 1 year (33). The most accurate
modality to date is combined leukocyte-marrow
scintigraphy, with an accuracy of over 90% (33).
A positive diagnosis of infection is made when
radiotracer uptake is present on the labeled
leukocyte scan with no corresponding marrow
uptake on the sulfur colloid scan (33). There has
also been substantial interest in using positron
emission tomography (PET) for this purpose, al-
though results have varied (34).
The variability in the accuracy of PET in de-
termining the presence of infection may be due
to differences in the criteria chosen (34). Pooled
studies have shown an overall accuracy of 90.4%
at the hip, which is the most relevant location in
patients with oncologic total knee reconstructions
requiring tibial and femoral stems (34). At the
hip, the site of activity appears to be more im-
Zbojniewicz and Sorger 735
Figure 15. Implant failure in a 19-
year-old man with a modular endo-
prosthesis. (a) Radiograph obtained
shortly after surgery shows correct
placement of the endoprosthesis.
(b) Radiograph obtained 2 weeks
later shows disruption at the level of
the rotating hinge (arrow).
portant than the standardized uptake value, with
uptake along the midshaft at the prosthesis-bone
interface being the most reliable indicator of in-
fection (Fig 14) (34).
Another cause of mechanical failure is implant
failure. Because of the frequent use of a con-
strained endoprosthesis for tumor surgery, there
is increased stress at the implant-bone interface
that increases the risk for implant failure (Fig 15)
(14,29).
Additional complications that are unique to
the expandable endoprosthesis include break-
age with unexpected shortening or lengthening
and outgrowing of the available extension of the
implant (10). There is also an increased risk of
infection with expandable implants due to the
need for a percutaneous procedure in minimally
invasive implants, with a reported increase in
the rate of infection of 0%–5% per procedure;
however, this figure is expected to decrease with
the growing use of newer noninvasive expandable
implants (10,30).
Complications seen with biologic reconstruc-
tion include nonunion, infection, and fracture.
Nonunion is arbitrarily defined as lack of union
by 1 year and is the most frequently encountered
complication in biologic reconstruction (Fig
16) (10,35). Nonunion occurs in 27%–32% of
patients receiving adjuvant chemotherapy, com-
pared with 11%–12% of patients not receiving
chemotherapy (36,37). Chemotherapy does not
affect the rate of infection, fracture, or amputa-
tion (36). Imaging studies evaluating the radio-
graphic appearances of osteoarticular and inter-
calary allografts showed a statistically significant
736 May-June 2014 radiographics.rsna.org

Figure 16. Nonunion of an

osteoarticular allograft in a 25-
year-old woman with a history
of proximal humeral osteosar­
coma. (a) CT image obtained
nearly 2 years after surgery
helps confirm a lack of bridg-
ing at the host-allograft junc-
tion (arrow). (b) On a radio-
graph (magnified view) of the
host-allograft junction obtained
following revision, the auto-
graft (bone placed around the
site to aid with future union)
(arrow) is faintly visible.

Figure 17. Sequelae of nerve transec-

tion in a 14-year-old girl with fibular
Ewing sarcoma. Axial T1-weighted MR
image obtained following resection,
which required sacrifice of the peroneal
nerve, shows selective fatty infiltration
and decreased muscle bulk of the an-
terior and lateral compartments of the
lower leg (arrows).

increase in the severity and duration of soft-tissue

swelling in patients with complications, suggest-
ing that subjective increased severity and dura-
tion of soft-tissue swelling lasting more than 6
months raises the possibility of infection (19,20).
Substantial graft bone resorption may also be as-
sociated with the presence of infection (16).
Surgical Treatment
of Soft-Tissue Tumors
Complications of surgery for soft-tissue tumors
are related to the nerve resection that is required
if involved with tumor or disease recurrence. At
MR imaging, the sequelae of nerve transection
can manifest acutely with a muscle edema pat-
tern related to denervation and chronically with
fatty infiltration and decreased muscle bulk (Fig
17). Traumatic neuromas following total tran-
section of the nerve are typically terminal-type
neuromas, with bulbous enlargement at the end
of the nerve (Fig 18) (38). These neuromas are
not true neoplasms, but instead represent an
attempted reparative proliferation of the nerve
tissue (38). They can arise 1–12 months follow-
ing the injury and can manifest with pain or be
asymptomatic (38).
Medical Treatment
Radiation therapy increases the clinical concern
for infection and poor wound healing. It also im-
pairs osteoblast function, which can manifest as
osteopenia and increase the risk for insufficiency
fractures (25).
Radiation-induced neoplasms are another po-
tential complication of radiation treatment and
may be benign or malignant. Osteochondromas
are benign radiation-induced neoplasms that can
occur after the administration of doses ranging
from 1600 to 6425 cGy; however, they typically
occur only if the patient undergoes radiation
therapy at a very young age (usually <2 years)
(25). In our experience, these neoplasms are seen
RG • Volume 34 Number 3 Zbojniewicz and Sorger 737

Figure 18. Traumatic terminal-type neu-

roma in a 13-year-old girl with prior resection
of an epithelioid sarcoma at the plantar foot.
On a sagittal fat-suppressed T1-weighted MR
image obtained with gadolinium-based con-
trast material, the end of the medial plantar
nerve (arrows) has a bulbous configuration.

most frequently in patients who have undergone
whole-body irradiation for neuroblastoma.
Malignant radiation-induced sarcomas can
develop after treatment of both benign and ma-
lignant tumors and may originate from either the
irradiated tumor or normal bone, although they
occur much more commonly in soft tissue than
in bone (ratio of 2.3:1) (22,25). The mean re-
ported dose is around 5000 cGy, and the latency
period can range from 4 to 30 years (mean, 8–12
years); however, osseous lesions tend to have
a longer latency period than soft-tissue lesions
(22,25). Undifferentiated pleomorphic sarcoma
(previously known as malignant fibrous histiocy-
toma) is the most common postirradiation soft-
tissue sarcoma and typically manifests with rapid
growth, whereas osteosarcoma is the most com-
mon histologic subtype arising from bone and
can manifest with aggressive bone destruction
and soft-tissue extension (22,25).
Local Disease Recurrence
Local recurrence is a leading concern following
limb salvage. The presence of local recurrence
in the setting of limb salvage is directly related
to surgical margins and the degree of tumor ne-
crosis following neoadjuvant therapy (10). Local
recurrence is also of concern following resection
of soft-tissue tumors.
MR imaging is commonly used to detect lo-
cal recurrence after limb salvage, demonstrat-
ing localized or nodular contrast enhancement;
however, false-positive results can occur due to
enhancing scar tissue, reactive hyperemia, or
capillary sprouting (39). In addition, the util-
ity of MR imaging is limited in patients with
metallic implants or fixation. Ultrasonography
can be a useful adjunct in this setting by helping
evaluate the soft tissues surrounding the metallic
hardware.
In soft-tissue tumors, disease recurrence is
typically seen at MR imaging as a discrete soft-
tissue nodule that often recapitulates the ap-
pearance of the original tumor; hence, review of
preoperative imaging findings can be beneficial
(Fig 19) (22). Axial pre- and postcontrast T1-
weighted imaging can be useful in distinguishing
between postoperative hemorrhagic change or
hematoma and tumor recurrence (22).
PET/CT has demonstrated a high sensitivity
for the detection of local recurrence in patients
with soft-tissue or bone sarcoma (Figs 20, 21)
(39–42). One study by Arush et al (40) was per-
formed exclusively in the setting of pediatric soft-
tissue and bone sarcoma. The authors defined
recurrence as any focal uptake of FDG higher
than normal background uptake that could not
be related to physiologic biodistribution of the
radiotracer or a known benign process. All seven
local recurrences were detected, yielding a sensi-
tivity of 100% and a specificity of 92%; the only
false-positive finding was related to infection
(40). Franzius et al (42) used similar criteria and
reported identical results; however, their study
consisted exclusively of patients with primary
bone sarcoma (either Ewing sarcoma or osteosar-
coma). A recent study by Al-Ibraheem et al (39)
of a mixture of adult and pediatric soft-tissue and
bone sarcomas found local recurrence in six of
seven patients (sensitivity = 86%), whereas con-
trast-enhanced CT had a sensitivity of only 43%.
Conclusion
Pediatric patients who are diagnosed with muscu-
loskeletal tumors often require serial imaging with
multiple imaging modalities; thus, it is important
to be familiar with the expected findings and com-
plications. Following curettage of a benign bone
lesion, gradual disappearance of the radiolucent
zone around a ceramic bone graft substitute is
indicative of healing, whereas the development
of radiolucency over time suggests recurrent dis-
ease. Osseous malignancies are most commonly
treated with limb salvage, which may consist of
endoprosthetic or biologic reconstruction. Major
complications associated with endoprostheses in-
clude (a) mechanical failure, which can often be
diagnosed on radiographs alone; and (b) infection,
which may be difficult to diagnose with any imag-
ing modality, although PET may play a role in the
future. Nonunion is the most common complica-
tion of biologic reconstruction and is generally
considered to be present when healing has not oc-
curred after 1 year. Local tumor recurrence often
738 May-June 2014 radiographics.rsna.org

Figure 19. Local tumor recurrence. (a) Axial fat-suppressed T1-weighted

MR image shows a homogeneously enhancing mass. The mass was subsequently
diagnosed as desmoid-type fibromatosis, and the patient underwent surgical re­
section. (b) Axial fat-suppressed T2-weighted MR image obtained approximately
2 weeks after surgery shows a recurrent mass with homogeneous hyperintensity.
(c) Axial postcontrast fat-suppressed T1-weighted MR image shows this same
mass with mildly thick-walled but peripheral enhancement, suggesting a post-
operative seroma. (d) Axial postcontrast fat-suppressed T1-weighted MR image
obtained approximately 6 months after surgery shows an enhancing mass (arrow)
whose pattern of enhancement is identical to that of the original mass, a finding that
is consistent with local recurrence.

Figures 20, 21. (20) Local tumor recurrence in a 17-year-old girl who had been treated surgically for sacral
osteo­­sarcoma. (a) Axial FDG PET image shows a focus of increased uptake (arrow) that is difficult to localize.
(b) Corresponding axial nonenhanced CT image from the PET/CT study shows the relationship of the area of FDG
uptake to the spine and psoas muscle, but the nodule (arrow) is not well seen. (c) Axial postcontrast fat-suppressed
T1-weighted MR image clearly shows an enhancing nodule (arrow), which proved to represent tumor recurrence.
(21) Local tumor recurrence in a 22-year-old man with a history of Ewing sarcoma. The patient had undergone
treatment that included radiation therapy. (a) Coronal FDG PET image shows a well-defined area of increased up-
take within the muscle tissue surrounding the left femur (arrows). This corresponds to the radiation portal and is
an expected posttreatment finding. No uptake is present in the femur itself. (b) Coronal FDG PET image obtained
5 months later shows new foci of uptake (arrow) in the prior biopsy tract, consistent with local tumor recurrence.
++(c) Nonenhanced CT image more clearly depicts the old biopsy tract (arrow).
RG • Volume 34 Number 3 Zbojniewicz and Sorger 739
740 May-June 2014
manifests at MR imaging as a nodular mass with
contrast enhancement in the resection bed, but
focal increased FDG uptake higher than normal
background uptake at PET has been shown to be
very sensitive for local recurrence and is comple-
mentary to MR imaging.
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Teaching Points May-June Issue 2014

Posttreatment Imaging of Pediatric Musculoskeletal Tumors

Andrew M. Zbojniewicz, MD • Joel I. Sorger, MD
RadioGraphics 2014; 34:724–740 • Published online 10.1148/rg.342135069 • Content Codes:

Page 725
The goal of treatment in benign bone tumors is removal of the tumor followed by the reestablishment of
bone morphology and structural support without compromising axial growth, joint function, or overall
morbidity.

Page 726
Ceramic material appears denser than adjacent native bone, and a thin, well-defined radiolucent zone
at the host-graft junction is an expected finding early after placement, but this radiolucent zone should
disappear as osseous ingrowth occurs.

Page 727
The goal of limb salvage surgery is to preserve the limb with adequate function without sacrificing overall
survival.

Page 731
Persistent or developing radiolucency—often at the margins of the graft—following graft placement may
indicate tumor recurrence or graft resorption without incorporation.

Page 735
Nonunion is arbitrarily defined as lack of union by 1 year and is the most frequently encountered compli-
cation in biologic reconstruction.