DOI:10.2214/AJR.07.2083
AJR 2007; 189:1203-1210
© American Roentgen Ray Society
Benign Nonphysiologic Lesions with Increased 18F-FDG Uptake on PET/CT: Characterization and Incidence
Ur Metser1,2,
Elka Miller2,
Hedva Lerman1 and
Einat Even-Sapir1
1 Department of Nuclear Medicine, Tel-Aviv Sourasky Medical Center, Sackler
Faculty of Medicine, 6 Weizman St., Tel-Aviv 64239, Israel.
2 Department of Radiology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of
Medicine, Tel-Aviv, Israel.
Received February 18, 2007;
accepted after revision June 5, 2007.
Address correspondence to U. Metser
(umetser{at}gmail.com).
Abstract
OBJECTIVE. The objective of our study was to characterize benign
lesions showing increased 18F-FDG uptake and to determine their
incidence on whole-body FDG PET/CT performed in oncologic patients. In
addition, the performance of PET alone and PET/CT in characterizing lesions as
benign was compared.
MATERIALS AND METHODS. A retrospective review of 1,134 consecutive
reports of PET/CT studies performed in patients with proven or suspected
malignancy over a 6-month period yielded 289 patients with 313 lesions that
showed increased FDG uptake but were suspected to be benign (nonphysiologic)
or indeterminate. Lesions were subjectively categorized on the basis of the
intensity of FDG uptake (mild, moderate, or marked) as compared with
background activity. For each lesion, a decision was made as to whether a
benign diagnosis could be obtained by the CT part of the study, the PET
pattern, or clinical correlation, or whether histologic sampling was
necessary. The performance of PET alone and PET/CT for characterizing lesions
as benign was compared. Two hundred twenty-nine of the lesions were assessed
further: 210 were benign and 19, malignant. The final diagnosis was determined
by pathology (n = 67), PET/CT follow-up (n = 58),
correlative imaging (n = 59), clinical correlation (n = 32),
or typical benign pattern on PET/CT (n = 13).
RESULTS. The causes for benign uptake of FDG were inflammatory
processes (n = 154, 73.3%), benign tumors (n = 23, 11%),
hematoma or seroma (n = 17, 8.1%), fracture (n = 7, 3.3%),
fat necrosis (n = 3, 1.4%), and others (n = 6, 2.9%). For
lesions with moderate or marked uptake of FDG (n = 117, 55.7%), a
benign diagnosis could have been suggested on either PET or CT (e.g., a
"hot" osteophyte) in 33 lesions (28.2%), on CT alone (e.g.,
peritoneal fat necrosis) in 38 lesions (32.5%), on PET alone (e.g.,
sialadenitis) in 10 lesions (8.5%), or by clinical correlation (e.g., dental
abscess) in four lesions (3.4%). A benign diagnosis could not be established
without histology (e.g., colonic polyp) in 32 lesions (27.4%). The performance
of PET/CT was superior to that of PET alone in characterizing lesions as
benign (p< 0.001).
CONCLUSION. Benign lesions with increased FDG uptake are found in
more than 25% of the PET/CT studies performed in patients with proven or
suspected malignancy, with inflammation being the most common cause. Lesion
characterization on the CT portion of the PET/CT study increases the
specificity of PET/CT reporting, especially for lesions with moderate or
marked FDG uptake.
Keywords: benign lesions • FDG PET • oncologic imaging • PET/CT • whole-body imaging
Introduction
There has been an ongoing increase in the routine clinical use of
18F-FDG PET for staging and follow-up of a wide range of oncologic
diseases. Although FDG PET is a sensitive imaging technique for the
identification of malignant tumors, FDG is not tumor-specific. Variable
physiologic sites of uptake may be seen in Waldeyer's tonsillar ring; along
the gastrointestinal tract; or in the orbital muscles, brain cortex,
myocardium, renal collecting systems, bladder, and gonads
[1]. FDG uptake in skeletal
muscles and in brown fat located in the neck, supraclavicular regions, axilla,
mediastinum, and retroperitoneum has been described as a potential physiologic
pitfall in FDG PET interpretation
[2–4].
In addition, the authors of multiple reports have described the uptake of FDG
in various nonphysiologic benign lesions, mostly inflammatory processes
[5].
The purpose of the current study was to characterize benign lesions showing
increased FDG uptake and to determine their incidence on whole-body FDG PET/CT
performed in oncologic patients. In addition, the performance of PET alone and
PET/CT in characterizing lesions as benign was compared.
Materials and Methods
Patient Population
A retrospective review of 1,134 consecutive reports of PET/CT studies
performed in patients with proven or suspected malignancy over a 6-month
period (between January and June 2003) yielded 289 patients with 313 lesions
that showed increased FDG uptake but were suspected to be benign
(nonphysiologic) or indeterminate. The patients included 152 females and 137
males who ranged in age from 1 to 85 years (mean, 58 years; median, 59 years).
Table 1 summarizes the
indications for PET/CT in these patients. Two hundred fifty-three of the
patients had a known malignancy and were referred for staging or follow-up.
The remaining 36 patients had no previously diagnosed malignancy and were
referred for evaluation of a lung mass (n = 26), lymphadenopathy
(n = 6), adrenal mass (n = 2), or nonspecific bone lesion
(n = 2) on conventional imaging.
Two hundred twenty-nine of the 313 lesions were assessed further. The
remaining patients were lost to follow-up, or the referring physician chose
not to request further assessment of the reported indeterminate or presumed
benign lesion, and a final diagnosis was not available. Of the lesions that
were assessed further, 19 (in 18 patients) were malignant and 210 (in 194
patients) were benign and represent the study cohort. The final diagnosis was
determined by pathology (n = 67), PET/CT follow-up (n = 58),
correlative imaging (n = 59), clinical correlation (n = 32),
or typical benign pattern on PET/CT (n = 13).
Malignant lesions were diagnosed histologically (n = 17) or by
clear progression of disease at the same site on follow-up PET/CT (n
= 2) (Table 2). Clinical
correlation enabled identification of multiple benign entities, including
dental abscesses, an infected sebaceous cyst, postoperative changes in the
chest or abdominal wall in patients examined within 1 month after surgery,
subcutaneous granulomas at a port insertion site or at injection sites, a
hematoma or seroma, a skin infection, and infectious mononucleosis with
positive serology for Epstein-Barr virus. Typical patterns on PET/CT included
FDG uptake around a hip replacement prosthesis, with a differential diagnosis
of loosening of the prosthesis or infection, as well as costochondritis,
bursitis, and tenosynovitis. These patterns have been previously described in
the literature [6,
7].
PET/CT Scanning
Patients were asked to fast for at least 4 hours before undergoing the
examination. All patients had glucose levels below 150 mg/dL. Patients
received an IV injection of 370–666 MBq (10–18 mCi) of FDG. Data
acquisitions were performed 60–120 minutes after injection using an
integrated in-line PET/CT system (Discovery LS, GE Healthcare). Iodinated oral
contrast material was administered for bowel opacification. Data acquisition
was as follows: CT was performed first from the head to the pelvic floor with
140 kV, 80 mA, a tube rotation time of 0.5 second, a pitch of 6, and a 5-mm
section thickness, which was matched to the PET section thickness. Immediately
after CT, a PET emission scan was obtained that covered the identical
transverse field of view. The acquisition time was 5 minutes for each table
position. PET image data sets were reconstructed iteratively using CT data for
attenuation correction, and coregistered images were displayed on a
workstation (Xeleris, GE Healthcare).
Lesion Analysis and Statistics
Studies were then analyzed by a panel of two experienced reviewers in
consensus. Lesions were subjectively categorized as showing mild, moderate, or
marked uptake on the basis of the intensity of FDG uptake compared with
background activity (Fig. 1A,
1B,
1C,
1D,
1E,
1F,
1G,
1H,
1I,
1J). For each lesion, a
decision was made as to whether a benign diagnosis could be obtained by the CT
part of the study, the PET pattern, or clinical correlation, or whether
histologic sampling was necessary.
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Fig. 1A —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (A), PET (B), and fused PET/CT
(C) images show marked uptake of FDG (arrows) (maximum
standardized uptake value = 8.1) in 57-year-old woman with histologically
proven bronchiolitis obliterans with organizing pneumonia.
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Fig. 1B —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (A), PET (B), and fused PET/CT
(C) images show marked uptake of FDG (arrows) (maximum
standardized uptake value = 8.1) in 57-year-old woman with histologically
proven bronchiolitis obliterans with organizing pneumonia.
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Fig. 1C —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (A), PET (B), and fused PET/CT
(C) images show marked uptake of FDG (arrows) (maximum
standardized uptake value = 8.1) in 57-year-old woman with histologically
proven bronchiolitis obliterans with organizing pneumonia.
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Fig. 1D —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (A), PET (B), and fused PET/CT
(C) images show moderate uptake of FDG (arrows) in 50-year-old
man with left adrenal adenoma that was stable for more than 2 years.
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Fig. 1E —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (A), PET (B), and fused PET/CT
(C) images show moderate uptake of FDG (arrows) in 50-year-old
man with left adrenal adenoma that was stable for more than 2 years.
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Fig. 1F —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (A), PET (B), and fused PET/CT
(C) images show moderate uptake of FDG (arrows) in 50-year-old
man with left adrenal adenoma that was stable for more than 2 years.
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Fig. 1G —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (G), PET (H), fused PET/CT (I),
and correlative fat-suppressed T2-weighted MR (J) images show mild
uptake of FDG (arrows, H–J) in 56-year-old woman with
neurofibroma involving C6–C7 nerve root.
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Fig. 1H —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (G), PET (H), fused PET/CT (I),
and correlative fat-suppressed T2-weighted MR (J) images show mild
uptake of FDG (arrows, H–J) in 56-year-old woman with
neurofibroma involving C6–C7 nerve root.
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Fig. 1I —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (G), PET (H), fused PET/CT (I),
and correlative fat-suppressed T2-weighted MR (J) images show mild
uptake of FDG (arrows, H–J) in 56-year-old woman with
neurofibroma involving C6–C7 nerve root.
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Fig. 1J —Composite figure of three patients showing mild, moderate, or
marked uptake of 18F-FDG in benign lesions as compared with
background activity. CT (G), PET (H), fused PET/CT (I),
and correlative fat-suppressed T2-weighted MR (J) images show mild
uptake of FDG (arrows, H–J) in 56-year-old woman with
neurofibroma involving C6–C7 nerve root.
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Lesions with moderate or marked FDG uptake are a subgroup of lesions for
which a benign diagnosis may be challenging and PET assessment alone may be
falsely positive for malignancy. For these lesions, the specificity of FDG PET
and fused PET/CT for correctly identifying lesions as benign was assessed and
compared using the McNemar test. A p value of < 0.05 was
considered statistically significant.
Results
Tables 3,
4,
5 summarize the body regions
and intensity of uptake of the 210 benign lesions. The causes for benign
uptake of FDG were inflammatory processes (n = 154, 73.3%), benign
tumors (n = 23, 11%), hematoma or seroma (n = 17, 8.1%),
fracture (n = 7, 3.3%), fat necrosis (n = 3, 1.4%), and
others (n = 6, 2.9%).
For the benign lesions with moderate or marked uptake of FDG (n =
117/210, 55.7%), a benign diagnosis could have been suggested on either PET or
CT (Fig. 2A,
2B,
2C) in 33 lesions (28.2%), on
CT alone (Fig. 3A,
3B,
3C,
3D,
3E,
3F) in 38 lesions (32.5%), on
PET alone (Fig. 4) in 10
lesions (8.5%), or by clinical correlation (e.g., dental abscess) in four
lesions (3.4%). A benign diagnosis could not be established without histology
(Fig. 5A,
5B,
5C) in 32 lesions (27.4%).
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Fig. 2A —Benign pattern suggested on both CT and PET in 41-year-old
man with Crohn's disease. CT (A), PET (B), and fused PET/CT
(C) images show marked uptake of 18F-FDG in long segment of
concentrically thickened distal ileum (arrows) with submucosal
deposition of fat, which is suggestive of inflammatory bowel disease. Crohn's
disease was confirmed on histology.
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Fig. 2B —Benign pattern suggested on both CT and PET in 41-year-old
man with Crohn's disease. CT (A), PET (B), and fused PET/CT
(C) images show marked uptake of 18F-FDG in long segment of
concentrically thickened distal ileum (arrows) with submucosal
deposition of fat, which is suggestive of inflammatory bowel disease. Crohn's
disease was confirmed on histology.
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Fig. 2C —Benign pattern suggested on both CT and PET in 41-year-old
man with Crohn's disease. CT (A), PET (B), and fused PET/CT
(C) images show marked uptake of 18F-FDG in long segment of
concentrically thickened distal ileum (arrows) with submucosal
deposition of fat, which is suggestive of inflammatory bowel disease. Crohn's
disease was confirmed on histology.
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Fig. 3A —CT pattern suggestive of benign diagnosis. CT (A), PET
(B), and fused PET/CT (C) images show abnormal uptake of
18F-FDG in enlarged distal external iliac node (arrows) on
right in 52-year-old man with lymphoma. Focal abnormal uptake of FDG in left
groin (arrowheads) is localized on CT to iliopsoas tendon, which is
consistent with tendinosis.
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Fig. 3B —CT pattern suggestive of benign diagnosis. CT (A), PET
(B), and fused PET/CT (C) images show abnormal uptake of
18F-FDG in enlarged distal external iliac node (arrows) on
right in 52-year-old man with lymphoma. Focal abnormal uptake of FDG in left
groin (arrowheads) is localized on CT to iliopsoas tendon, which is
consistent with tendinosis.
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Fig. 3C —CT pattern suggestive of benign diagnosis. CT (A), PET
(B), and fused PET/CT (C) images show abnormal uptake of
18F-FDG in enlarged distal external iliac node (arrows) on
right in 52-year-old man with lymphoma. Focal abnormal uptake of FDG in left
groin (arrowheads) is localized on CT to iliopsoas tendon, which is
consistent with tendinosis.
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Fig. 3D —CT pattern suggestive of benign diagnosis. CT (D), PET
(E), and fused PET/CT (F) images show focal uptake of FDG in
left flank (arrows) in 70-year-old man. Fused PET/CT image (F)
shows uptake to be in small soft-tissue-attenuation mass with fat-attenuation
center suggestive of fat necrosis, which was proven histologically.
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Fig. 3E —CT pattern suggestive of benign diagnosis. CT (D), PET
(E), and fused PET/CT (F) images show focal uptake of FDG in
left flank (arrows) in 70-year-old man. Fused PET/CT image (F)
shows uptake to be in small soft-tissue-attenuation mass with fat-attenuation
center suggestive of fat necrosis, which was proven histologically.
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Fig. 3F —CT pattern suggestive of benign diagnosis. CT (D), PET
(E), and fused PET/CT (F) images show focal uptake of FDG in
left flank (arrows) in 70-year-old man. Fused PET/CT image (F)
shows uptake to be in small soft-tissue-attenuation mass with fat-attenuation
center suggestive of fat necrosis, which was proven histologically.
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Fig. 5A —Histologic diagnosis necessary to define benign lesion in
59-year-old man. CT (A), PET (B), and fused PET/CT (C)
images show abnormal uptake of 18F-FDG in polypoid lesion
(arrows) along right wall of rectum. Resected specimen (not shown)
revealed tubulovillous adenoma with no evidence of malignancy.
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Fig. 5B —Histologic diagnosis necessary to define benign lesion in
59-year-old man. CT (A), PET (B), and fused PET/CT (C)
images show abnormal uptake of 18F-FDG in polypoid lesion
(arrows) along right wall of rectum. Resected specimen (not shown)
revealed tubulovillous adenoma with no evidence of malignancy.
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Fig. 5C —Histologic diagnosis necessary to define benign lesion in
59-year-old man. CT (A), PET (B), and fused PET/CT (C)
images show abnormal uptake of 18F-FDG in polypoid lesion
(arrows) along right wall of rectum. Resected specimen (not shown)
revealed tubulovillous adenoma with no evidence of malignancy.
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Performance of PET Alone and PET/CT
For the 117 lesions with moderate or marked uptake of FDG, for which a
benign diagnosis on PET alone may be challenging, PET alone correctly
identified 43 lesions as benign with a specificity of 37%, whereas PET/CT
correctly identified 81 lesions as benign with a specificity of 69%
(p < 0.001). When taking into account clinical correlation as an
adjunct to characterizing lesions as benign, the specificities of PET and
PET/CT improve to 40% and 73%, respectively (p < 0.001).
Discussion
A systematic review of consecutive PET/CT studies performed over a 6-month
period showed that benign nonphysiologic uptake of FDG was encountered in more
than 25% of the studies. Almost three quarters of these lesions were
inflammatory. In more than half of the benign nonphysiologic sites of
increased FDG uptake, the intensity of uptake may be moderate or marked
compared with background activity, making a benign diagnosis with PET alone
challenging, with a potentially high incidence of false-positive
interpretations. The complexity of image interpretation is confounded by
potential physiologic uptake of FDG along the gastrointestinal tract and the
overlap in the degree of FDG uptake in benign and malignant tumors involving
certain organs, such as the thyroid, adrenal glands, or colon. In addition,
after surgery, the degree of FDG uptake in inflammatory processes,
postsurgical change, and recurrent tumor may also overlap.
Several studies have shown that fusion of PET data with CT improves not
only the sensitivity of PET but also its specificity
[8,
9]. The advantage of PET/CT
over PET alone can be attributed to the low anatomic resolution of PET and the
difficulty in lesion localization on PET. Morphologic data from CT may assist
in improving the diagnostic accuracy of nonspecific lesions with increased FDG
uptake
[9–11].
Although an argument could be made that PET scans are often interpreted
side-by-side with correlative imaging, several studies have shown that
interpreting fused PET/CT images has an advantage over the former review
method. Pelosi et al. [10]
reported that for lesion localization alone, PET/CT had ambiguous findings for
only 3.4% of lesions compared with 15.3% with PET and correlative imaging
(p < 0.0001). In an additional study, investigators assessing 168
lesions in oncology patients found localization was incorrect in almost 10% of
lesions despite side-by-side correlation with CT. Furthermore, fused imaging
has been found to be superior for the assessment of small lesions; lesions
adjacent to chest or abdominal wall; and lesions adjacent to mobile organs
such as the diaphragm, the mesentry, or loops of bowel
[8].
In the current study, although PET alone or PET and clinical correlation
could suggest a benign diagnosis for some of the benign lesions with moderate
or marked uptake of FDG (39% and 40%, respectively), CT localization and
characterization on fused PET/CT images helped to correctly classify an
additional one third of lesions as benign. In certain instances, such as
pulmonary Langerhans cell histiocytosis, lipoid pneumonia, epiploic
appendagitis, or abdominal fat necrosis (secondary to surgery, trauma, or
pancreatitis), CT findings are pathognomonic or are at least highly suggestive
[12–14]
(Figs. 3A,
3B,
3C,
3D,
3E,
3F and
6A,
6B,
6C,
6D,
6E,
6F,
6G,
6H,
6I). Because FDG uptake in
these lesions may be high, they may simulate tumor on PET: Lipoid pneumonia
may appear as a malignant lung tumor, the multiple nodules in Langerhans cell
histiocytosis may appear as lung metastases, and fat necrosis may falsely be
interpreted as a metastatic peritoneal deposit or as local tumor
recurrence.
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Fig. 6A —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT image obtained using lung window setting
(A), PET image (B), and zoomed CT image obtained using
soft-tissue window setting (C) show marked uptake of FDG
(arrows) in subpleural mass in left lower lobe of lung in 77-year-old
woman. Zoomed CT image shows fat attenuation in center of mass, which is
suggestive of lipoid pneumonia.
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Fig. 6B —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT image obtained using lung window setting
(A), PET image (B), and zoomed CT image obtained using
soft-tissue window setting (C) show marked uptake of FDG
(arrows) in subpleural mass in left lower lobe of lung in 77-year-old
woman. Zoomed CT image shows fat attenuation in center of mass, which is
suggestive of lipoid pneumonia.
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Fig. 6C —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT image obtained using lung window setting
(A), PET image (B), and zoomed CT image obtained using
soft-tissue window setting (C) show marked uptake of FDG
(arrows) in subpleural mass in left lower lobe of lung in 77-year-old
woman. Zoomed CT image shows fat attenuation in center of mass, which is
suggestive of lipoid pneumonia.
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Fig. 6D —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT (D), PET (E), and fused PET/CT
(F) images. CT image shows multiple cysts (thin arrow,
D) and nodules (thick arrow, D) in both lung fields in
61-year-old man. PET and fused PET/CT images show abnormal uptake of FDG in
nodule (arrows, E and F). Findings are suggestive of
Langerhans cell histiocytosis, which was confirmed on biopsy.
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Fig. 6E —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT (D), PET (E), and fused PET/CT
(F) images. CT image shows multiple cysts (thin arrow,
D) and nodules (thick arrow, D) in both lung fields in
61-year-old man. PET and fused PET/CT images show abnormal uptake of FDG in
nodule (arrows, E and F). Findings are suggestive of
Langerhans cell histiocytosis, which was confirmed on biopsy.
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Fig. 6F —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT (D), PET (E), and fused PET/CT
(F) images. CT image shows multiple cysts (thin arrow,
D) and nodules (thick arrow, D) in both lung fields in
61-year-old man. PET and fused PET/CT images show abnormal uptake of FDG in
nodule (arrows, E and F). Findings are suggestive of
Langerhans cell histiocytosis, which was confirmed on biopsy.
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Fig. 6G —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT (G), PET (H), and fused PET/CT
(I) images show marked masslike abnormal uptake of FDG
(arrows) on PET image in 53-year-old man. CT shows lung infiltrate
thought to represent pneumonia. Infiltrate resolved on CT performed after
antibiotic therapy (not shown).
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Fig. 6H —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT (G), PET (H), and fused PET/CT
(I) images show marked masslike abnormal uptake of FDG
(arrows) on PET image in 53-year-old man. CT shows lung infiltrate
thought to represent pneumonia. Infiltrate resolved on CT performed after
antibiotic therapy (not shown).
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Fig. 6I —Composite figure of three patients with benign lung lesions
on 18F-FDG PET/CT. CT (G), PET (H), and fused PET/CT
(I) images show marked masslike abnormal uptake of FDG
(arrows) on PET image in 53-year-old man. CT shows lung infiltrate
thought to represent pneumonia. Infiltrate resolved on CT performed after
antibiotic therapy (not shown).
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Some of the benign lesions encountered in our patient population were
benign tumors (11%). CT and correlative radiography may confirm a benign
lesion, as was the case with one adrenal adenoma (with attenuation values of
< 10 H on unenhanced CT) and one enchondroma of the femur. However, in more
than 27% of benign tumors with moderate or marked uptake of FDG, biopsy was
necessary for final diagnosis. Biopsy was needed in cases of focal FDG uptake
in the thyroid, the colon, or an intrabronchial polyp because the degree of
FDG uptake and the morphologic appearance of the lesions could not be used to
reliably confirm or exclude malignancy. Similarly, lymph nodes with
significant uptake of FDG due to inflammatory or infectious conditions may
also require histologic sampling. The only exception may be for symmetric
uptake of FDG in hilar and mediastinal lymph nodes due to lymphoid follicular
hyperplasia secondary to smoking or chronic pulmonary disease. On CT, these
nodes may contain calcifications or may show higher attenuation values than
the surrounding great vessels. A previous study examining the performance of
FDG PET/CT in staging non–small cell lung cancer showed that
histologically nodes with this appearance on CT were reactive with follicular
hyperplasia in the cortex and showed anthracotic pigmentation with macrophage
infiltration in the medulla
[15].
The common denominator for the majority (> 73%) of benign lesions
showing abnormal uptake of FDG in this study was active inflammation, whether
infectious, such as mycobacterial infection, or noninfectious, such as
postsurgical granulomas or osteoarthritis. Increased uptake of FDG in
inflammation may be explained by the recruitment of activated WBCs
(granulocytes, lymphocytes, and macrophages). These cells have been found to
have enhanced levels of glucose transporters (GLUTs), especially GLUT 3 and,
to a lesser extent, GLUT 1
[16], and to have an increased
affinity to deoxyglucose through various cytokines and growth factors. For
example, tumor necrosis factor 
is a cytokine produced primarily by
monocytes and has been shown to activate macrophages in experimental models of
inflammation as well as clinically in rheumatoid arthritis or as a response to
bacterial endotoxins [17,
18]. Activated monocytes
directly activate reduced nicotinamide adenine dinucleotide phosphate (NADPH)
oxidase, which imposes an acute metabolic demand met by an increased use of
both internal energy stores and exogenous metabolites such as glucose
[19,
20]. Recently, in vitro
studies have shown that activation of monocytes without further activation of
NADPH oxidase is sufficient to increase glucose metabolism
[19]. These pathophysiologic
processes may explain the increased uptake of FDG encountered in active
inflammatory processes.
In conclusion, benign lesions with increased FDG uptake are common, found
in more than one quarter of PET/CT studies performed, with inflammation being
the most common cause. Precise lesion localization and characterization on the
CT portion of the PET/CT study improve the specificity of PET/CT reporting,
especially for lesions with moderate or marked FDG uptake that may easily be
mistaken for tumor.
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Abstract
Introduction
