AJR 2004; 183:1133-1141
© American Roentgen Ray Society
Nonneoplastic Diseases in the Chest Showing Increased Activity on FDG PET
Peter V. Kavanagh1,
Aaron W. Stevenson1,
Michael Y. Chen1 and
Paige B. Clark1
1 All authors: Department of Radiology, Wake Forest University School of
Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1088.
Received November 6, 2003;
accepted after revision March 9, 2004.
Address correspondence to P. V. Kavanagh.
Introduction
PET with glucose analogue 18F-FDG shows increased glucose
metabolism in metabolically active processes and has been well documented to
be a sensitive and specific technique for evaluating and staging patients with
thoracic malignancies [1,
2]. Inflammatory or infectious
processes can also have increased FDG activity leading to a diagnostic
dilemma, and increased FDG activity has been shown in more than 40 different
benign conditions [1,
3]. This review is a
compilation of cases describing a spectrum of nonneoplastic intrathoracic
diseases associated with increased FDG activity on PET confirmed at biopsy or
surgery or on the basis of findings on follow-up imaging. Visual, qualitative
analysis of 18F-FDG activity was performed for all lesions. In
equivocal cases, quantitative analysis using standardized uptake values based
on a lean body mass algorithm was performed. A standardized uptake value
threshold of 2.5 was used to delineate malignant-range activity on PET
[4].
Infections
Mycobacterium avium-intracellulare
Mycobacterium avium-intracellulare is a common cause of
nontuberculous mycobacteria infection in immunocompromised, late middle-aged,
and elderly patients and in those with chronic lung disease. CT appearances in
the late middle-aged and elderly typically produce a combination of
bronchiectasis and lung nodules. The nodules may grow over time, raising
concern for malignancy. Thus, imaging studies can be nonspecific, and
percutaneous needle biopsy may be indicated. On occasion, the diagnosis may be
obtained only after surgical intervention. M.
avium-intracellulare has previously been shown to have diffuse,
intense FDG activity on PET
[5]. Focal intense areas of FDG
activity may also be shown (Figs.
1A,
1B, and
1C).
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Fig. 1A. —Mycobacterium avium-intracellulare infection in
53-year-old man with cough and 20-pack-year smoking history. CT scan shows
spiculated noncalcified right upper lobe lung nodule and emphysema.
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Fig. 1B. —Mycobacterium avium-intracellulare infection in
53-year-old man with cough and 20-pack-year smoking history. Axial (B)
and coronal (C) PET images show increased FDG activity
(arrows) at right upper lobe lesion. Less intense focus of activity
in left upper lobe (arrowhead, C) corresponded with smaller
lung nodule present on higher CT slice (not shown). M.
avium-intracellulare infection was isolated from CT-guided percutaneous
biopsy of right upper lobe nodule. Both lesions resolved on follow-up imaging
(not shown) after antimicrobial therapy.
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Fig. 1C. —Mycobacterium avium-intracellulare infection in
53-year-old man with cough and 20-pack-year smoking history. Axial (B)
and coronal (C) PET images show increased FDG activity
(arrows) at right upper lobe lesion. Less intense focus of activity
in left upper lobe (arrowhead, C) corresponded with smaller
lung nodule present on higher CT slice (not shown). M.
avium-intracellulare infection was isolated from CT-guided percutaneous
biopsy of right upper lobe nodule. Both lesions resolved on follow-up imaging
(not shown) after antimicrobial therapy.
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Mycotic Pseudoaneurysm
Unusual complications of infections, such as mycotic pseudoaneurysm, may
also result in diagnostic difficulty. Mycotic pseudoaneurysms are uncommon but
their imaging features can be confused with malignant tumors. On CT, a
soft-tissue mass surrounding the aneurysm is a recognized sign of mycotic
aneurysm (Figs. 2A,
2B, and
2C). However, perivascular
neoplastic lesions can produce similar appearances.
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Fig. 2A. —Mycotic pseudoaneurysm in 80-year-old woman with chest pain.
CT scan without contrast material could not distinguish mediastinal mass
invading aortic wall from contained rupture due to penetrating atherosclerotic
ulcer.
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Fig. 2B. —Mycotic pseudoaneurysm in 80-year-old woman with chest pain.
On axial (B) and coronal (C) PET images, lesion shows increased
FDG activity (arrows) with central photopenia adjacent to aorta,
suspicious for necrotic tumor. At surgery, purulent mass was found adjacent to
aneurysmal defect in aortic arch. Pathologic analysis revealed evidence of
pseudoaneurysm, although culture showed Escherichia coli. Aorta was
successfully repaired intraoperatively.
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Fig. 2C. —Mycotic pseudoaneurysm in 80-year-old woman with chest pain.
On axial (B) and coronal (C) PET images, lesion shows increased
FDG activity (arrows) with central photopenia adjacent to aorta,
suspicious for necrotic tumor. At surgery, purulent mass was found adjacent to
aneurysmal defect in aortic arch. Pathologic analysis revealed evidence of
pseudoaneurysm, although culture showed Escherichia coli. Aorta was
successfully repaired intraoperatively.
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Inflammatory Conditions
Cryptogenic Organizing Pneumonia
Cryptogenic organizing pneumonia, formerly known as bronchiolitis
obliterans with organizing pneumonia, can have a distinctive radiographic
pattern, and multiple bilateral opacities are a common finding on chest
radiography (Figs. 3A,
3B,
3C,
3D, and
3E). CT shows a characteristic
peribronchovascular or peripheral predominance of air-space opacities and may
show small nodules and areas of ground-glass attenuation. Foci of decreased
attenuation within consolidations are not commonly seen in patients with
cryptogenic organizing pneumonia and raise the possibility of abscess
formation or malignancy with necrosis.
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Fig. 3B. —Cryptogenic organizing pneumonia in 58-year-old woman with
cough and intermittent low-grade fever for 3 months. CT scans show
peripherally distributed air-space opacities (arrow, B) and
nodule (arrowhead, C).
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Fig. 3C. —Cryptogenic organizing pneumonia in 58-year-old woman with
cough and intermittent low-grade fever for 3 months. CT scans show
peripherally distributed air-space opacities (arrow, B) and
nodule (arrowhead, C).
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Fig. 3D. —Cryptogenic organizing pneumonia in 58-year-old woman with
cough and intermittent low-grade fever for 3 months. PET was performed in
attempt to identify lesion with potentially highest yield for biopsy. Axial
PET images show increased FDG activity (arrows) in air-space opacity.
Cryptogenic organizing pneumonia was confirmed by percutaneous biopsy. Patient
recovered after several relapses, which occurred when steroids were
discontinued.
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Fig. 3E. —Cryptogenic organizing pneumonia in 58-year-old woman with
cough and intermittent low-grade fever for 3 months. PET was performed in
attempt to identify lesion with potentially highest yield for biopsy. Axial
PET images show increased FDG activity (arrows) in air-space opacity.
Cryptogenic organizing pneumonia was confirmed by percutaneous biopsy. Patient
recovered after several relapses, which occurred when steroids were
discontinued.
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Sarcoidosis
Sarcoidosis is a multisystem disease of unknown cause that is characterized
by the presence of noncaseating granulomas. Chest radiographs may show normal
findings or evidence of bihilar or mediastinal lymphadenopathy. The most
frequent lung manifestations are fine nodular, acinar, or reticulonodular
opacities and rarely appear as a pure miliary pattern. On CT, mediastinal and
bihilar lymphadenopathy are commonly seen, with multiple small nodules in a
perilymphatic distribution (Figs.
4A and
4B). In addition, areas of
ground-glass attenuation may be seen with irregular thickening of
bronchovascular bundles and interlobular septa.
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Fig. 4B. —Sarcoidosis in 32-year-old man complaining of lack of energy
and exercise intolerance. Coronal PET image shows abnormal FDG activity in
same distribution (arrows). Bronchoscopy with transbronchial biopsy
was performed. Pathology showed noncaseating granulomas consistent with
sarcoidosis. Normal cardiac activity is noted (arrowhead).
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Round Atelectasis
Round atelectasis is a common entity that can be difficult to differentiate
from neoplasm on cross-sectional imaging. The characteristic comet-tail sign,
adjacent pleural thickening, and volume loss may not always be present. In one
series [6], all round
atelectasis lesions were negative on FDG PET. Thus, FDG PET can play an
important role in differentiating round atelectasis from malignancy,
particularly when few or atypical signs of radiofrequency ablation are seen on
imaging studies.
Vascular Diseases
Atherosclerosis
Atherosclerosis is a progressive disorder that may be associated with an
inflammatory component. This may explain why PET activity is often increased
in atherosclerotic foci [7]. In
patients with aortic atherosclerosis, FDG activity can be seen in a linear
distribution or with focal nodules corresponding to atherosclerotic plaque in
the descending thoracic aorta (Figs.
5A and
5B).
Pulmonary Embolic Disease
Most pulmonary emboli encountered in clinical practice are thromboemboli
consisting of fibrin-platelet aggregates. However, other sources of emboli may
occur, such as fat, amniotic fluid, tumor, air, or exogenous material such as
a radionuclide (Figs. 6A,
6B, and
6C).
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Fig. 6B. —FDG embolism in 67-year-old man with coronary artery disease.
Axial (B) and coronal (C) PET images show no FDG activity in
nodule. Focus of intense activity (standardized uptake value = 49) was present
in right lung (arrows) without corresponding CT abnormality. It was
postulated this discrepancy represented artifact because it had no anatomic
correlation with recent CT. In addition, standardized uptake value was high,
suggesting area of concentrated FDG. Follow-up PET image obtained 1 week later
(not shown) revealed resolution of FDG activity. Part of administered FDG
likely clumped with platelet aggregate during administration, forming embolus
that traveled to lung. This finding could also be due to intercurrent
infection if CT was remote.
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Fig. 6C. —FDG embolism in 67-year-old man with coronary artery disease.
Axial (B) and coronal (C) PET images show no FDG activity in
nodule. Focus of intense activity (standardized uptake value = 49) was present
in right lung (arrows) without corresponding CT abnormality. It was
postulated this discrepancy represented artifact because it had no anatomic
correlation with recent CT. In addition, standardized uptake value was high,
suggesting area of concentrated FDG. Follow-up PET image obtained 1 week later
(not shown) revealed resolution of FDG activity. Part of administered FDG
likely clumped with platelet aggregate during administration, forming embolus
that traveled to lung. This finding could also be due to intercurrent
infection if CT was remote.
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Pneumoconioses
Silicosis is an occupational lung disease in which nodules of collagen form
in response to inhaled silica. Coalescence of multiple small nodules results
in massive fibrosis. The radiographic pattern consists of multiple small
nodules that are usually well circumscribed and of uniform density, often with
hilar lymph node enlargement. Characteristic CT findings consist of focal
soft-tissue masses with irregular margins. These lesions may grow slowly over
time, raising concern for tumors. PET can be markedly positive in cases of
progressive massive fibrosis, likely because of inflammatory cell activity
occurring at the time of the study (Figs.
7A,
7B, and
7C).
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Fig. 7A. —Progressive massive fibrosis secondary to silicosis in
57-year-old man with history of colorectal carcinoma and 20-pack-year smoking
history. CT scan shows spiculated bilateral upper lobe masses.
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Fig. 7B. —Progressive massive fibrosis secondary to silicosis in
57-year-old man with history of colorectal carcinoma and 20-pack-year smoking
history. Axial (B) and coronal (C) PET images show abnormal FDG
activity (arrows) in masses. Biopsy confirmed progressive massive
fibrosis.
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Fig. 7C. —Progressive massive fibrosis secondary to silicosis in
57-year-old man with history of colorectal carcinoma and 20-pack-year smoking
history. Axial (B) and coronal (C) PET images show abnormal FDG
activity (arrows) in masses. Biopsy confirmed progressive massive
fibrosis.
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Immunologic Conditions
Eosinophilic granuloma is a variant of Langerhans cell histiocytosis that
may involve the lung and has significantly higher prevalence among patients
who smoke cigarettes. This disease predominantly affects the upper and mid
lung zones, often with characteristic sparing of the costophrenic angles
[8]. Early on, the radiographic
appearance consists of a nodular or reticulonodular pattern. A proportion of
cases progress with the development of fibrosis, sometimes leading to
end-stage lung disease. Common abnormalities seen on CT are the presence of
irregularly shaped cysts and nodules (Figs.
8A and
8B). It is useful to know that
nodules caused by eosinophilic granuloma can show increased FDG activity on
PET, similar to neoplastic nodules. Therefore, when the imaging features of
eosinophilic granuloma are atypical, percutaneous biopsy is indicated because
of the lack of specificity of PET in this situation.
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Fig. 8A. —Eosinophilic granuloma in 64-year-old woman with colon
cancer. CT scan shows dominant left upper lobe nodule (arrowhead)
with numerous smaller pulmonary nodules (straight arrows) and cysts
(curved arrow) scattered throughout both lungs.
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Fig. 8B. —Eosinophilic granuloma in 64-year-old woman with colon
cancer. Coronal PET image shows increased FDG activity (arrow) in
region of large nodule seen on CT. Smaller nodules are likely below PET
resolution.
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Trauma
Bone fractures, particularly when acute or during the active healing phase,
can show increased FDG activity on PET (Figs.
9A,
9B, and
9C). When conventional
radiographic evaluation fails to identify the fracture, CT (viewed on
appropriate bone window settings) is useful to confirm the diagnosis. A
fracture with a significant soft-tissue or destructive component on CT is
suspicious for a pathologic fracture, and such lesions often need to be
biopsied for histologic assessment. Soft-tissue injuries may also be FDG-avid,
although typically the standardized uptake value interpretations will not be
in the malignant range. This may be a reflection of the inflammation that can
be associated with soft-tissue injuries.
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Fig. 9A. —52-year-old man with history of malignant melanoma. Chest
radiograph shows focal opacity in lateral right hemithorax (arrow),
suggestive of metastatic disease. Asterisk indicates large hiatal hernia.
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Fig. 9B. —52-year-old man with history of malignant melanoma. Coronal
PET image shows focal area of increased FDG activity (arrow)
corresponding to radiographic abnormality. Normal cardiac activity
(arrowhead) is noted.
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Fig. 9C. —52-year-old man with history of malignant melanoma. Chest CT
scan reveals rib fracture in lateral right chest wall (arrow). No
soft-tissue or destructive component is associated with this fracture, and no
other abnormality is detected in this region.
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Iatrogenic Conditions
FDG avidity related to various forms of therapy can be seen in the thorax
and elsewhere in the body. Increased FDG activity on PET is well recognized
for up to 6 months after surgery. Radiation therapy can also cause increased
FDG activity (Figs. 10A and
10B).
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Fig. 10A. —48-year-old man with Hodgkin's disease, who had completed
radiation therapy 9 months previously. Chest CT scan reveals bilateral
juxtamediastinal fibrotic changes (arrows) typical of chronic
radiation pneumonitis. No significant lymphadenopathy is present.
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Fig. 10B. —48-year-old man with Hodgkin's disease, who had completed
radiation therapy 9 months previously. Axial PET image shows diffuse FDG
activity (standardized uptake value = 1.9) in fibrotic areas
(arrows).
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Physiologic and Congenital Processes
Supraclavicular Brown Fat
Bilateral supraclavicular FDG activity is a common finding in patients
undergoing PET. In the past, this activity was often attributed to malignancy,
muscle uptake, inflammation, or infection, but recent studies show that 28% of
supraclavicular activity is caused by brown fat uptake
[9]. Small amounts of brown fat
surround the blood vessels of the mediastinum, neck, and retrocrural area. CT
confirmation of areas of fat and no involvement of lymph nodes or muscle is
necessary [9] (Figs.
11A and
11B).
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Fig. 11B. —Supraclavicular brown fat uptake in 9-year-old boy with
lymphoma. Coronal PET image shows increased FDG activity in supraclavicular
regions. Note physiologic FDG activity (arrow) in heart.
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Hamartoma
Pulmonary hamartomas may be single or multiple and consist mainly of masses
of cartilage with clefts lined by bronchial epithelium. They sometimes contain
foci of fat. Typically, hamartomas are spherical or slightly lobulated,
well-defined nodules with normal surrounding lung with spotty or linear
calcifications. CT may show a nodule with calcific or fat density. However,
failure to detect calcium or fat does not preclude the diagnosis. PET may show
increased activity (Figs. 12A,
12B, and
12C), leading to concern for
malignancy in certain patients. In these patients, invasive procedures such as
percutaneous biopsy may be required to establish the diagnosis.
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Fig. 12A. —Hamartoma in 66-year-old woman with history of colon cancer
metastatic to liver. CT scan shows irregularly marginated nodule in right
lower lobe (arrow). No calcification or fat was shown in this nodule
on CT.
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Fig. 12B. —Hamartoma in 66-year-old woman with history of colon cancer
metastatic to liver. Axial (B) and coronal (C) PET images show
increased activity in nodule (arrows). Subsequent percutaneous needle
biopsy revealed pulmonary hamartoma.
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Fig. 12C. —Hamartoma in 66-year-old woman with history of colon cancer
metastatic to liver. Axial (B) and coronal (C) PET images show
increased activity in nodule (arrows). Subsequent percutaneous needle
biopsy revealed pulmonary hamartoma.
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Conclusions
The uptake of FDG with PET in nonneoplastic thoracic diseases may limit the
evaluation of patients with pulmonary malignancy. Knowledge of the conditions
with positive FDG uptake will provide accurate diagnosis and avoid unnecessary
treatments. Close correlation between CT and PET allows the most accurate
radiologic differential diagnosis.
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Introduction
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