AJR 2004; 182:983-989
© American Roentgen Ray Society
False-Positive FDG Positron Emission Tomography Uptake in Nonmalignant Chest Abnormalities
Syed Asad1,
Suzanne L. Aquino2,
Nitra Piyavisetpat2 and
Alan J. Fischman2
1 Department of Neurology, Emory University Hospital, 1639 Pierce Dr., WMRB
6009, Atlanta, GA 30322.
2 Department of Radiology, Massachusetts General Hospital, 55 Fruit St., FND
202, Boston, MA 02114.
Received June 4, 2003;
accepted after revision August 20, 2003.
Address correspondence to S. L. Aquino
(saquino{at}partners.org).
Introduction
Positron emission tomography (PET) with FDG monitors the enhanced
glycolytic activity and increased expression of glucose transporters
associated with tumor cells. FDG accumulates in tumors via the same
transporters used by glucose. Similarly, once in the cell, the radiotracer is
phosphorylated to FDG-6PO4. At this point the handling of FDG
differs from glucose. Because of the lack of an oxygen at the 2-position in
FDG, it cannot proceed further in glycolysis or glycogen synthesis and becomes
a "trapped tracer." This characteristic of FDG has led to its
widespread use for whole-body imaging of patients with cancer. Also, because
of the relatively long physical half-life of fluorine-18, it can be
distributed to imaging facilities without on-site cyclotrons.
In general, the clinical evaluation of glucose metabolism of FDG is based
on qualitative inspection or semiquantitative analysis of region-of-interest
values or lesion radioactivity normalized to the injected dose and body weight
(standard uptake value). Qualitative inspection focuses on the identification
of abnormal regions of increased uptake greater than the background blood pool
(as gauged by mediastinal uptake). Semiquantitative analysis has been cited
and implemented with variable results because of its reliance on steady-state
conditions for glucose uptake and metabolism. Conditions such as blood glucose
and insulin levels and the number of transporters on a specific tumor cell
(which is not generally known) have a large impact on diseased and nondiseased
soft-tissue uptake and should be taken into consideration
[1].
Infectious and inflammatory lesions may have increased FDG accumulation and
mimic tumor. In most cases these findings are attributed to the increased
metabolic state of accumulated inflammatory cells. For instance, studies have
shown that the positive predictive value of PET in detecting metastatic lung
cancer in mediastinal lymph nodes is only 72%
[1]. False-positive mediastinal
lymph node findings at histopathology were from nodes with reactive
hyperplasia, granulomatous diseases, or silicosis
[2]. This pictorial essay
reviews nonmalignant diseases of the lungs and mediastinum that may show
increased uptake greater than mediastinal background and therefore mimic
neoplasia.
Pulmonary Hamartoma
Pulmonary hamartoma is a benign neoplasm that contains normal pulmonary
tissue including bronchi, cartilage, and fat. CT findings such as internal fat
or popcornlike calcifications help distinguish a hamartoma from a malignancy.
However, in those nodules in which only soft tissue is present, the radiologic
diagnosis is impossible (Fig.
1A,
1B).
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Fig. 1B. —59-year-old man with pulmonary mass. FDG positron emission
tomography image shows increased uptake (arrow) suggestive of
neoplasm. Surgical pathology revealed bronchial cartilaginous hamartoma.
Theoretically, hamartoma should not show increased uptake of FDG. In this
example, when FDG is increased, further diagnosis by biopsy or resection is
warranted.
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Pneumonia
Granulocytes and macrophages use glucose as an energy source. When these
cells are activated through infection, their metabolism and thus FDG uptake
increase. Pulmonary inflammation and pneumonia can manifest increased
glycolysis and, as a result, FDG uptake
[3]. Pneumonia, either acute or
organizing, may show increased uptake of FDG and resemble malignancy
especially if the infection is focal in distribution (Fig.
2A,
2B).
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Fig. 2B. —67-year-old man with newly diagnosed pulmonary nodule. FDG
positron emission tomography image shows increased uptake (arrow)
suggestive of malignancy. Nodule was resected and showed organizing
pneumonia.
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Caseating Granulomas
Caseating granulomas develop with mycobacterial or fungal infections and
involve the pulmonary lymph nodes and parenchyma. Histologically,
granulomatous lesions are characterized by central caseous necrosis surrounded
by inflammatory cellular infiltrates. Activated inflammatory and phagocytic
cells have markedly increased metabolism and a rate of glycolysis 20–30
times greater than baseline values
[4]. On FDG PET, actively
infected granulomatous nodules will show increased FDG metabolism (Fig.
3A,
3B).
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Fig. 3B. —62-year-old man with history of lung cancer and severe
emphysema. FDG positron emission tomography image of thorax shows increased
radiotracer uptake of FDG in nodule (arrow). Wedge resection was
performed. Nodule was caused by atypical mycobacterial infection.
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Sarcoidosis
Sarcoidosis is a systemic granulomatous inflammatory disorder that may
affect any organ, but most commonly involves the respiratory tract.
Noncaseating granulomas involve the lymph nodes and lungs. Active inflammatory
cells (epithelioid histiocytes, multinucleated giant cells, lymphocytes,
plasma cells, and fibroblasts) in these granulomas will show increased uptake
of FDG on PET [5] (Figs.
4A,
4B and
5). Elevated pulmonary glucose
use and FDG uptake in pulmonary sarcoidosis may return to normal after steroid
therapy.
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Fig. 4B. —69-year-old woman with multiple pulmonary nodules. FDG
positron emission tomography image shows multiple foci of increased uptake
(arrows) in lungs. Biopsy showed epithelioid granulomas consistent
with sarcoidosis.
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Fig. 5. —24-year-old woman with newly diagnosed lymphadenopathy in
thorax. FDG positron emission tomography image shows multiple areas of
increased uptake in mediastinal and hilar lymph nodes (arrows).
Surgical biopsy showed sarcoidosis. Diffuse FDG uptake in enlarged thoracic
lymph nodes suggests lymphoma. Presence of lymphadenopathy combined with
parenchymal abnormalities in bilateral upper lobe distribution suggests
sarcoidosis.
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Amyloidosis
Amyloidosis includes a spectrum of diseases associated with the abnormal
extracellular deposition of amyloid, a proteinaceous material that appears as
green birefringence with Congo red stain under polarized light. Amyloidosis in
the thorax may affect the tracheobronchial tree, pulmonary parenchyma as
nodules or interstitial disease, heart, and pleura. On CT, amyloid pulmonary
nodules tend to have sharp margins, contain calcifications, are multiple in
number, and measure up to several centimeters
[6]. Associated parenchymal
disease includes thin-walled cysts that are the sequelae of small airway
occlusion and air trapping. Figure
6A,
6B shows a case of
biopsy-proven nodular pulmonary amyloid and moderate glucose metabolism on
PET.
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Fig. 6A. —72-year-old woman with history of breast cancer and newly
diagnosed pulmonary nodules. CT scan shows multiple nodules (arrows)
and associated parenchymal cysts (arrowheads). Some nodules contain
calcium.
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Fig. 6B. —72-year-old woman with history of breast cancer and newly
diagnosed pulmonary nodules. FDG positron emission tomography image shows
increased uptake in nodule (arrow) in right lower lobe. This nodule
was biopsied and showed amyloid on Congo red stain.
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Talc Pleurodesis
Pleurodesis is commonly used in the management of malignant pleural
effusions. After pleurodesis, the pleural space develops variable degrees of
pleural thickening and nodularity (some of which is caused by tumor) on CT,
often with a residual loculated effusion. Dense talc may deposit in nodules
that accumulate in the parietal pleura
[7]. These talc nodules may
resemble pleural calcifications or plaques. Talc stimulates a chronic
granulomatous reaction and may be FDG-avid and thus mimic tumor recurrence on
PET (Fig. 7A,
7B).
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Fig. 7A. —68-year-old woman with history of breast cancer and talc
pleurodesis 10 years earlier. CT scan shows dense nodular pleural thickening
(arrows) in right lower thorax adjacent to esophagus and inferior
vena cava.
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Fig. 7B. —68-year-old woman with history of breast cancer and talc
pleurodesis 10 years earlier. FDG positron emission tomography (PET) image
shows increased uptake in nodules (arrows). CT scan should be
available to correlate areas of hypermetabolism on PET with regions of dense
talc deposits to avoid false-positive interpretation. These nodules were
stable on sequential CT scans for more than 5 years.
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Round Atelectasis
Round atelectasis is a benign inflammatory process caused by the involution
of lung in a region of chronic pleural thickening. Round atelectasis is
associated with asbestos pleural disease, tuberculous effusions, hemothorax,
or any other chronic pleural process
[8].
On CT, round atelectasis usually manifests as a 2- to 7-cm round or oval
mass in a subpleural location with adjacent pleural effusion or thickening,
swirling vessels and bronchi feeding into the mass (comet-tail sign), and
volume loss in the affected lobe. Round atelectasis is usually not
metabolically active on FDG PET despite its inflammatory nature
[8]. Increased uptake warrants
biopsy or resection to exclude a malignancy (Fig.
8A,
8B).
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Fig. 8A. —68-year-old man with pulmonary nodule and history of asbestos
pleural disease. CT scan shows 3-cm subpleural nodule (arrow) in
right upper lobe adjacent to pleural plaque (arrowhead).
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Fig. 8B. —68-year-old man with pulmonary nodule and history of asbestos
pleural disease. FDG positron emission tomography image of upper thorax shows
increased uptake in nodule (arrow). This nodule was resected, and
pathologic findings were consistent with round atelectasis.
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Pleural Fibrosis
Pleural fibrosis and plaques may develop from asbestos or beryllium
exposure, prior hemothorax, empyema, or thoracotomy. They are usually less
than 1 cm thick and often calcify. Multifocal pleural plaques can form because
of asbestos or beryllium exposure and tend to be bilateral.
An important differential diagnosis for asbestos-related pleural disease is
malignant pleural mesothelioma. Figure
9A,
9B shows diffuse, increased
uptake in the pleura suggestive of malignancy. Surgical biopsy, however,
confirmed benign inflammation.
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Fig. 9B. —71-year-old man with weight loss and chronic heart disease.
Coronal FDG positron emission tomography image shows increased uptake
(arrows) in right pleura. Surgical biopsy showed organizing fibrinous
pleuritis and fibrosis in pleura. No malignancy was found.
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Atherosclerosis
Atherosclerosis is a chronic inflammatory response to endothelial injury in
which macrophages and lymphocytes accumulate in mural plaques. Previous
reports have shown increased uptake of FDG in the vasculature of patients at
high risk for atherosclerotic disease
[9]. Focal vascular uptake in
the mediastinum may mimic metastatic lymph node disease on PET (Fig.
10A,
10B,
10C). In such instances, CT
correlation (and fusion imaging, if available) would be helpful for anatomic
clarification.
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Fig. 10A. —60-year-old woman with lung cancer. FDG positron emission
tomography (PET) image shows multiple areas of increased uptake
(arrows) in superior mediastinum suggestive of diffuse nodal
disease.
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Fig. 10C. —60-year-old woman with lung cancer. CT scan without fusion of
PET image of vascular anatomy shows contrast-enhanced left common carotid
artery (arrow). Mediastinoscopy confirmed no evidence of mediastinal
metastatic disease.
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Conclusion
This pictorial essay reviews nonmalignant diseases of the lung, pleura, and
mediastinum that are caused by infectious or inflammatory processes and that
may show increased FDG PET uptake. In many instances, CT findings may also be
suspicious for malignancy. A diagnostic biopsy is therefore indicated to reach
a definitive diagnosis.
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Introduction
Pulmonary Hamartoma
