AJR Integrative Imaging

1.5 CME
1.0 SAM

LIFELONG LEARNING
FOR RADIOLOGY

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Musculoskeletal Pitfalls in 18F-FDG PET/CT:

Self-Assessment Module
Colleen M. Costelloe1, William A. Murphy, Jr.1, Beth A. Chasen2

ABSTRACT
Identification of pitfalls is essential to the correct interpretation of 18F-FDG PET/CT. The educational objectives
of this self-assessment module are for the participant to exercise, self-assess, and improve his or her knowledge of FDG
PET/CT of the musculoskeletal system.

INTRODUCTION
This self-assessment module on musculoskeletal pitfalls in
FDG PET/CT has an educational component and a self-assessment component. The educational component consists of
two required articles that the participant should read. The
self-assessment component consists of 10 multiple-choice
questions with solutions. All of these materials are available
on the ARRS Website (www.arrs.org). To claim CME and
SAM credit, each participant must enter his or her responses
to the questions online.

EDUCATIONAL OBJECTIVES
By completing this activity, the participant will:
A. Exercise, self-assess, and improve his or her understanding of the musculoskeletal system as it pertains to FDG
PET/CT.
B. Exercise, self-assess, and improve his or her understanding of pitfalls pertaining to FDG PET/CT of the musculoskeletal system, stressing conditions that mimic metastases in bone and soft tissue.

REQUIRED READING
1. Costelloe CM, Murphy WA Jr, Chasen BA. Musculoskeletal pitfalls in 18F-FDG PET/CT: pictorial review. AJR
2009; 193[suppl]:S25; [web]WS1WS13
2. Peh WC, Khong PL, Yin Y, et al. Imaging of pelvic insufficiency fractures. RadioGraphics 1996; 16:335348

RECOMMENDED READING
1. Meller J, Sahlmann CO, Liersch T, Hao Tang P, Alavi A.
Nonprosthesis orthopedic applications of (18)F fluoro2-deoxy-D-glucose PET in the detection of osteomyelitis. Radiol Clin N Am 2007; 45:719733, viiviii
2. Shin DS, Shon OJ, Byun SJ, Choi JH, Chun KA, Cho

IH. Differentiation between malignant and benign pathologic fractures with F-18-fluoro-2-deoxy-D-glucose
positron emission tomography/computed tomography.
Skeletal Radiol 2008; 37:415421
3. Beckers C, Ribbens C, Andre B, et al. Assessment of disease activity in rheumatoid arthritis with (18)F-FDG
PET. J Nucl Med 2004; 45:956964
4. Schmitz A, Risse JH, Grunwald F, Gassel F, Biersack
HJ, Schmitt O. Fluorine-18 fluorodeoxyglucose positron
emission tomography findings in spondylodiscitis: preliminary results. Eur Spine J 2001; 10:534539
5. Schulte M, Brecht-Krauss D, Heymer B, et al. Grading
of tumors and tumorlike lesions of bone: evaluation by
FDG PET. J Nucl Med 2000; 41:16951701
6. Feldman F, Van Heertum R, Saxena C, Parisien M.
18
FDG-PET applications for cartilage neoplasms. Skeletal Radiol 2005; 34:367374
7. Schulte M, Brecht-Krauss D, Heymer B, et al. Fluoro
deoxyglucose positron emission tomography of soft tissue tumours: is a noninvasive determination of biological activity possible? Eur J Nucl Med 1999; 26:599605
8. McCarthy EF, Sundaram M. Heterotopic ossification: a
review. Skeletal Radiol 2005; 34:609619

INSTRUCTIONS
1. Complete the educational and self-assessment components included in this issue.
2. Visit www.arrs.org and log in.
3. Select Self-Assessment Modules from the Lifelong Learning box in the lower left of the page.
4. Add the SAM to your shopping cart and order the online
SAM as directed. (The SAM, including questions, must
be ordered to be accessed even though the activity is free
to ARRS members.) After purchasing the SAM, click on
OK; you will be returned to the ARRS home page.
5. Click on the My Education tab at the top of the page,
then on My Online Products. (Note: You must be logged
in to access this personalized page.)
6. You can also access the purchased SAM by logging on to
http://edu.arrs.org/myProducts/.
7. Answer the questions online to obtain SAM credit.

Keywords: FDG, musculoskeletal imaging, PET/CT, pitfalls

DOI:10.2214/AJR.09.7178
Received November 14, 2008; accepted after revision February 9, 2009.
1
Division of Diagnostic Imaging, Department of Diagnostic Radiology, Section of Musculoskeletal Radiology, The University of Texas M. D. Anderson Cancer Center,
1515 Holcombe Blvd., Houston, TX 77030. Address correspondence to C. M. Costelloe.
2

Division of Diagnostic Imaging, Department of Nuclear Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX.

AJR 2009;193:S26S30 0361803X/09/1933S26 American Roentgen Ray Society

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AJR:193, September 2009

Musculoskeletal Pitfalls in PET/CT

QUESTION 1

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Which of the following is TRUE regarding 18F-FDG?

A. It most commonly enters the cell through the
GLUT-10 glucose transporter.
B. It is phosphorylated by ATPase (adenosine tri
phosphatase) after entering the cell.
C. It rarely enters malignant cells through tumorelaborated glucose transporters.
D. It has been found in macrophages surrounding tumors.

QUESTION 2

C. Loss of white cortical endplates.

D. Pain.

QUESTION 6
Which of the following benign neoplastic
processes of bone is MOST likely to be correctly
identified as benign on the basis of FDG uptake?
A.
B.
C.
D.

Which of the following is TRUE regarding the

FDG uptake of fractures on PET/CT?
A. Most are obscured by the color field representing
FDG uptake on fused PET/CT images.
B. An undisplaced fracture line can be obscured on
the soft-tissue windows of the unfused CT images.
C. Malignant fractures show less FDG uptake than
benign fractures.
D. The standardized uptake value (SUV) reported in a
study conducted at one facility can be automatically
applied to PET scans obtained at other facilities.

QUESTION 3
Which of the following is TRUE regarding pelvic
insufficiency fractures?
A. They are common in cancer patients undergoing
radiation therapy but not chemotherapy.
B. They characteristically extend through the acetabula.
C. They are typically oblique in orientation.
D. They might not be properly identified without
reviewing multiple imaging planes.

QUESTION 4
Which arthropathy is MOST likely to be
conspicuously avid?
A.
B.
C.
D.

Synovial osteochondromatosis.
Osteoarthritis.
Active rheumatoid arthritis.
Treated rheumatoid arthritis.

QUESTION 5
Which is the BEST indicator of the presence
of infectious spondylodiskitis?
A. High FDG uptake.
B. Disk space narrowing.

AJR:193, September 2009

Enchondroma.
Aneurysmal bone cyst.
Giant cell tumor of the bone.
Fibrous dysplasia.

QUESTION 7
Which of the following is TRUE regarding
cartilage tumors?
A. Low-grade chondrosarcomas are typically
more FDG-avid than giant cell tumors of
bone.
B. Enchondromas are typically more avid than giant
cell tumors of bone.
C. Low-grade chondrosarcomas are typically more
avid than high-grade chondrosarcomas.
D. High-grade chondrosarcomas are typically more
avid than low-grade chondrosarcomas.

QUESTION 8
Which of the following is MOST likely to be
asymmetrically hypometabolic in the shoulder
on FDG PET/CT?
A. The supraspinatus muscle after a rotator cuff tear.
B. The supraspinatus muscle after rotator cuff
repair.
C. The greater tuberosity of the humerus after a
rotator cuff tear.
D. The greater tuberosity of the humerus after
rotator cuff repair.

QUESTION 9
On the basis of FDG uptake alone, each of the
following soft-tissue tumors could be mistaken
for malignancy EXCEPT:
A.
B.
C.
D.

Nodular fasciitis.
Lipoma.
Aggressive fibromatosis.
Pigmented villonodular synovitis.

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Costelloe et al.

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QUESTION 10
After falling off a ladder, a 20-year-old man
developed a masslike swelling in the distal anterior left thigh.The swelling failed to resolve.
Six weeks later, PET/CT showed an FDG-avid
intramuscular mass with peripheral calcification.
What is the MOST likely diagnosis?
A.
B.
C.
D.

Osteosarcoma.
Myositis ossificans.
Nodular fasciitis.
Gossypiboma.

Solution to Question 1
GLUT-1 is the most ubiquitously expressed of the glucose transporters and is considered the most common method by which glucose (or the glucose analogue, FDG) is
transported to the cell [1]. Although GLUT-10 exists, option A is not the best response. Once inside the cell, FDG is
phosphorylated by hexokinase, resulting in intracellular accumulation because the phosphorylated FDG molecule is
not a proper substrate for the glycolytic cycle. ATPases are
enzymes that convert ATP to ADP + P (adenosine diphosphate + phosphorus), thereby releasing energy that is used
to drive numerous cellular functions. Option B is not the
best response. The cause of strong FDG uptake in many
primary cancers is considered to be the overexpression of
tumor-elaborated glucose transporters. Option C is not the
best response. GLUT-1 upregulation has been discovered in
inflammatory cells and granulation tissue surrounding tumor in an animal model [2] and may account for residual
FDG uptake after successful cancer therapy. A small amount
of residual avidity does not necessarily prevent a diagnosis
of complete response to therapy. When in doubt, follow-up
PET/CT or biopsy can be performed to confirm a complete
response. Option D is the best response.

Solution to Question 2
Most fracture lines can be visualized on fused images despite the superimposed color field representing FDG uptake. Nevertheless, a minority are obscured by this color
field and must be viewed on the unfused CT data set for correct identification of the cause of the uptake. Option A is
not the best response. Viewing images in soft-tissue window
settings can obscure fine bony detail, such as an undisplaced
fracture line, that is otherwise readily appreciated on bone
window settings. Option B is the best response. Malignant
fractures are likely to show higher FDG uptake than benign
fractures [3]. Option C is not the best response. The same
study also found that malignant fractures were more likely
to exhibit marrow uptake, whereas FDG uptake was more

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likely to be confined to the cortex in benign fractures. A

potential confounding factor in this study regarding this particular conclusion was that most malignant fractures were located in the long bones, whereas most benign fractures were in
the axial skeleton [3]. Option D is not the best response because acquisition techniques must be identical among the different facilities to permit direct application of an absolute
numeric value such as the SUV. Nevertheless, the numeric values reported in studies are valuable because concepts such as
high or low uptake and proportionate differences in uptake
between comparable abnormalities, such as malignant and
benign fractures, can be applied.

Solution to Question 3
Although radiation therapy can lead to osteoradionecrosis
and an increased risk of fracture, chemotherapy can produce
osteopenia, which also puts patients at risk. Option A is not
the best response. Stress fractures can be divided into two
types. Insufficiency fractures occur when normal stress is applied to abnormal bone, and fatigue fractures occur when
abnormal stress, such as repetitive athletic activity, is applied
to normal bone. Therefore, anything that weakens bone can
predispose to an insufficiency fracture. In the pelvis, insufficiency fractures are characteristically found in the sacral ala,
the adjacent iliac bones, the pubic bodies, and the pubic rami
[4]. The acetabulum is not as common a location. Option B is
not the best response. Insufficiency fractures of the pelvis are
most readily identified by their vertical and linear orientation. Option C is not the best response. This pattern is easily
appreciated in the sacral ala and iliac bones and may or may
not be evident in the smaller pubic bones. A horizontal fracture can extend through the sacrum. When seen in combination with bilateral sacral alar fractures, an H-shaped configuration of severe involvement can be observed. Option D is the
best response because the linear nature of a fracture line may
not be apparent in a single plane. Complete evaluation of an
area of FDG uptake often requires viewing multiple planes
to ascertain the appearance of its long axis. Appreciation of
the overall shape and orientation of an abnormality can provide valuable diagnostic clues to its cause.

Solution to Question 4
Synovial osteochondromatosis is usually mildly avid. Option A is not the best response. An osteoarthritic joint may
be extremely or mildly avid, depending on the presence or
absence of synovitis. Therefore, option B is not the best response. High FDG avidity has been shown to positively correlate with active rheumatoid arthritis, as determined by
the signs and symptoms of the disease and the thickness of
the synovium on ultrasound. Option C is the best response.
Conversely, uptake has been shown to diminish with successful therapy. This makes FDG PET/CT an effective indicator of treatment response in patients with rheumatoid
arthritis [5]. Option D is not the best response.

AJR:193, September 2009

Musculoskeletal Pitfalls in PET/CT

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Solution to Question 5
Although FDG uptake is high in untreated spondylodiskitis [6], it is nonspecific and can be seen in nonemergent
conditions such as osteophyte or Schmorls node formation.
Option A is not the best response. Infectious spondylodiskitis rapidly destroys the disk itself, producing disk space narrowing. Nevertheless, narrowing is commonly found in degenerative disk disease, which is much more common than
infectious spondylodiskitis. Option B is not the best response. Loss of white cortical endplates is the classic indication of infectious spondylodiskitis on x-ray-based imaging.
On the CT portion of the PET/CT examination, endplate
destruction is typically best observed on sagittal, unfused
bone windows. Fused or soft-tissue windows may obscure
fine bony detail and prevent detection of this crucial finding. Option C is the best response. Although pain is expected
in patients with infectious spondylodiskitis, it is nonspecific
and can also have other causes such as metastatic disease,
insufficiency fracture, and inflammatory or degenerative
conditions. Option D is not the best response.

Solution to Question 6
Benign cartilaginous lesions of bone, such as enchondromas, can be FDG-avid. Although any focus of FDG uptake
in bone can be mistaken for a malignancy, none was sufficiently avid to be confused with malignancy in a study by
Schulte et al. [7]. Option A is the best response. Despite their
cystic nature, aneurysmal bone cysts may show FDG uptake high enough to be confused with a malignancy on the
basis of PET alone. The morphologic appearance of aneurysmal bone cyst is often characteristic and can be appreciated on the CT portion of the examination; radiographs of
all bone tumors are recommended because they are often
essential in characterizing lesions. Aneurysmal bone cysts
are expansile radiolucent lesions that are most commonly
found in the metaphysis of the long bones of skeletally immature individuals; the epiphyses are usually open. These
cysts show well-defined margins that may or may not be
sclerotic, and they show no matrix mineralization. No softtissue nodularity is seen centrally or in the rim of the cavity
on contrast-enhanced MRI. Option B is not the best response. Giant cell tumors of the bone are often highly FDGavid, and their morphologic features are distinctive, as
mentioned in the accompanying article [8]. They are typically found in skeletally mature individuals with closed epiphyses. Giant cell tumors of the bone are often cystic or
hemorrhagic on contrast-enhanced MRI and can be further
distinguished from aneurysmal bone cysts by the presence
of nodular soft-tissue components. Option C is also not the
best response. Fibrous dysplasia is another benign and often FDG-avid bone tumor. Option D is not the best response. Lesions of fibrous dysplasia are typically located in
the metaphyseal region of long bones and show well-defined
sclerotic rims. They are centrally located in the marrow

AJR:193, September 2009

cavity and may expand the bone. Matrix mineralization

can vary from complete absence (radiolucence) to mature
(heavy mineralization). Mild ground-glass mineralization is
part of the spectrum and may be present in all or part of
the lesion but is not necessary for diagnosis.

Solution to Question 7
Giant cell tumors are often highly FDG-avid, whereas
low-grade chondrosarcomas may show low avidity [7]. Option A is not the best response. Enchondromas tend to show
low FDG avidity [7]. Option B is not the best response.
Small studies comparing low-grade chondrosarcomas with
enchondromas have found the malignancies to be more avid
than benign cartilage tumors [9, 10]. Option B is not the
best response. Higher-grade chondrosarcomas are typically
more avid than those of lower grade [9]. Option C is not the
best response. Although some benign conditions may be
more avid than lower-grade chondrosarcomas, cartilage tumors have been observed to follow a progression of increasing FDG avidity with increasing histologic grade. This
trend is as expected, considering that more aggressive tumors often require greater amounts of glucose than less aggressive ones. Option D is the best response.

Solution to Question 8
When there is no mechanical loading on a muscle, it undergoes atrophy, which explains the emergent need for radiologists to inform clinicians of the presence of complete,
full-thickness tendon tears. Without sufficient load, muscles
diminish in size and develop fatty atrophy. Once atrophy is
advanced, muscle function is irrevocably lost and repair is
no longer an option. Before successful reattachment, the
muscles in one study [11] showed lower FDG uptake than
those on the normal contralateral side. Option A is the best
response. After successful repair, the muscle may increase in
FDG avidity, as has been reported through the return of
symmetric FDG uptake [11]. Option B is not the best response. FDG uptake has been seen at the insertion of rotator cuff muscles onto the greater tuberosity of the humerus
in patients with injury [12]. Option C is not the best response. FDG uptake on the greater tuberosity can also be
present after rotator cuff repair. The most commonly injured tendon is the supraspinatus; tears occur most frequently at its insertion onto the greater tuberosity of the
humerus. The repaired tendon is often fixed to the insertion
site by means of suture anchors drilled into the bone. Surgical trauma can therefore help explain FDG uptake in this
area. Option D is not the best response.

Solution to Question 9
Simple lipomas are composed of adipose tissue with possible thin septa lacking nodular soft-tissue components and
show minimal to no FDG uptake [13, 14]. Option B is the
best response. Nodular fasciitis, aggressive fibromatosis,

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Costelloe et al.

and pigmented villonodular synovitis were all found to

show sufficiently high FDG uptake to be confused with malignancy in a study conducted by Schulte et al. [14]. Options A, C, and D are not the best responses. Unlike bone
tumors, soft-tissue tumors often lack diagnostic features on
CT or radiography. An exception is low-grade adipose tumors, such as lipoma, because they contain a large amount
of fat that is readily identified because of low attenuation
(negative Hounsfield unit measurements). The CT portion
of a PET/CT study may be helpful in anatomically localizing abnormalities, such as to the joint itself in pigmented
villonodular synovitis. MRI is often able to differentiate between physiologic muscle uptake and tumor by confirming
or excluding the presence of a mass. This is possible through
the greater soft-tissue contrast resolution of MRI as compared with CT. Biopsy is necessary to identify the histology
of most soft-tissue lesions.

Solution to Question 10
Osteosarcoma is the most common nonhematologic primary
tumor of the bone and has a typical age range of 1525 years.
These tumors are FDG-avid, most commonly found in the
metaphysis of long bones such as the distal femur, permeate
the cortex in an aggressive fashion, and usually produce large
soft-tissue masses. Rarely, osteosarcoma arises in soft tissue
an extraskeletal osteosarcomarather than in bone. Osteoid
matrix mineralization is fluffy or cloudlike in appearance. The
matrix mineralization is most abundant internally rather than
at the periphery of the tumor. Option A is not the best response.
Myositis ossificans may be surrounded by muscle or form directly adjacent to bone. When adjacent to bone, it may initially
produce an inflammatory reaction, such as periostitis or bone
marrow edema, but it does not destroy cortex. Radiologically
and histologically, the correct diagnosis of myositis ossificans
depends on the identification of a zonal pattern of maturation
that recapitulates bone. A distinctive pattern of peripheral ossification is characteristic of mature myositis ossificans [15].
Before formation of rim ossification, amorphous calcifications
scattered in the mass may be mistaken for the matrix mineralization of a sarcoma. Postponing imaging until 6 weeks after
mass formation may spare the patient an unnecessary biopsy,
particularly when a history of trauma exists. Option B is the

best response. Although nodular fasciitis can be FDG-avid, it

does not produce rim-ossified masses. Option C is not the best
response. A foreign body reaction could be considered if the trauma involved an open wound. Nevertheless, the term gossypiboma specifically indicates a retained surgical implement, and no
history of surgery is given. Option D is not the best response.
References
1. Meller J, Sahlmann CO, Liersch T, Hao Tang P, Alavi A. Nonprosthesis orthopedic applications of (18)F fluoro-2-deoxy-D-glucose PET in the detection of
osteomyelitis. Radiol Clin North Am 2007; 45:719733, viiviii
2. Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral
distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in
macrophages and granulation tissues studied by microautoradiography. J Nucl
Med 1992; 33:19721980
3. Shin DS, Shon OJ, Byun SJ, Choi JH, Chun KA, Cho IH. Differentiation between malignant and benign pathologic fractures with F-18-fluoro-2-deoxy-Dglucose positron emission tomography/computed tomography. Skeletal Radiol
2008; 37:415421
4. Peh WC, Khong PL, Yin Y, et al. Imaging of pelvic insufficiency fractures.
RadioGraphics 1996;16:335348
5. Beckers C, Ribbens C, Andre B, et al. Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Nucl Med 2004; 45:956964
6. Schmitz A, Risse JH, Grunwald F, Gassel F, Biersack HJ, Schmitt O. Fluorine-18 fluorodeoxyglucose positron emission tomography findings in spondylodiscitis: preliminary results. Eur Spine J 2001; 10:534539
7. Schulte M, Brecht-Krauss D, Heymer B, et al. Grading of tumors and tumorlike
lesions of bone: evaluation by FDG PET. J Nucl Med 2000; 41:16951701
8. Costelloe CM, Murphy WA Jr, Chasen BA. Musculoskeletal pitfalls in 18FFDG PET/CT: pictorial review. AJR 2009; 193[suppl]:S25; [web]WS1WS13
9. Aoki J, Watanabe H, Shinozaki T, Tokunaga M, Inoue T, Endo K. FDG-PET in
differential diagnosis and grading of chondrosarcomas. J Comput Assist Tomogr 1999;23:603608
10. Feldman F, Van Heertum R, Saxena C, Parisien M. 18FDG-PET applications for
cartilage neoplasms. Skeletal Radiol 2005; 34:367374
11. Shinozaki T, Takagishi K, Ohsawa T, Yamaji T, Endo K. Pre- and postoperative
evaluation of the metabolic activity in muscles associated with ruptured rotator
cuffs by F-FDG PET imaging. Clin Physiol Funct Imaging 2006; 26:338342
12. Wandler E, Kramer EL, Sherman O, Babb J, Scarola J, Rafii M. Diffuse FDG
shoulder uptake on PET is associated with clinical findings of osteoarthritis.
AJR 2005; 185:797803
13. Suzuki R, Watanabe H, Yanagawa T, et al. PET evaluation of fatty tumors in the
extremity: possibility of using the standardized uptake value (SUV) to differentiate benign tumors from liposarcoma. Ann Nucl Med 2005; 19:661670
14. Schulte M, Brecht-Krauss D, Heymer B, et al. Fluorodeoxyglucose positron
emission tomography of soft tissue tumours: is a non-invasive determination of
biological activity possible? Eur J Nucl Med 1999; 26:599605
15. McCarthy EF, Sundaram M. Heterotopic ossification: a review. Skeletal Radiol
2005; 34:609619

F O R YO U R I N F O R M AT I O N

The readers attention is directed to the Pictorial Review article on which this SAM is based, which can be found online at WS1WS13.

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AJR:193, September 2009