DOI:10.2214/AJR.07.7001
AJR 2008; 190:S1-S6
© American Roentgen Ray Society
Imaging Features of Sarcoidosis on MDCT, FDG PET, and PET/CT
Hima B. Prabhakar1,
Chad B. Rabinowitz1,
Fiona K. Gibbons2,
Walter J. O'Donnell2,
Jo-Anne O. Shepard3 and
Suzanne L. Aquino3
1 Abdominal Imaging and Interventional Radiology, Department of Radiology,
Massachusetts General Hospital, 55 Fruit St., FND 270, Boston, MA 02114.
2 Department of Pulmonary/Critical Care Medicine, Massachusetts General
Hospital, Boston, MA.
3 Thoracic Radiology, Department of Radiology, Massachusetts General Hospital,
Boston, MA.
Received March 8, 2007;
accepted after revision June 11, 2007.
Address correspondence to H. B. Prabhakar
(himaprab{at}gmail.com).
Abstract
Objective
The objectives of this article are to discuss the epidemiology and natural
history of sarcoidosis; to review the classic imaging features of sarcoidosis
on radiography, CT, and 67Ga nuclear medicine scans; and to present
clinical examples of sarcoidosis as seen on PET and PET/CT in the chest,
abdomen and pelvis, and bones.
Conclusion
The imaging features of sarcoidosis are diverse and can be seen on a
variety of imaging techniques. It is important for radiologists and nuclear
medicine physicians to recognize the common imaging features and patterns of
sarcoidosis in order to raise the possibility in the appropriate clinical
setting.
Keywords: CT • FDG PET • MDCT • PET/CT • sarcoidosis
Introduction
Sarcoidosis is a multiorgan granulomatous disease with a wide variety of
imaging features. Imaging abnormalities can commonly be seen on chest
radiography, MDCT, 67Ga scans, FDG PET, and PET/CT. FDG uptake from
sarcoidosis is nonspecific and can mimic other disease processes, including
lymphoma and diffuse metastatic disease. When combined with imaging features
on other techniques, such as MDCT, FDG uptake can be useful in monitoring
therapeutic response in patients with known sarcoidosis. Because imaging
features of sarcoidosis can overlap considerably with those of malignant
disorders, it is important for both radiologists and nuclear medicine
specialists to be aware of the many varied presentations of sarcoidosis in
order to suggest the diagnosis in the appropriate clinical setting.
Sarcoidosis is a systemic and chronic disease of unknown cause
[1]. The characteristic
histologic lesion, a noncaseating granuloma, has been described as affecting
all organ systems, although they are most frequently seen affecting the lungs
[2].
The imaging features of sarcoidosis are protean and can be shown with a
variety of imaging techniques. Diagnostic imaging can not only help suggest a
diagnosis in asymptomatic patients, but can also help in monitoring
therapeutic response in symptomatic patients. FDG uptake on PET in patients
with sarcoidosis is nonspecific and can mimic that in malignancies such as
lymphoma and diffuse metastatic disease
[2].
Epidemiology
Sarcoidosis has a worldwide distribution and typically affects young to
middle-aged adults. The highest prevalence of the disease is found in
African-Americans, Swedes, and Danes. In the United States, the incidence rate
of sarcoidosis is 35.5 cases per 100,000 in blacks and 10.9 cases per 100,000
in whites. Additionally, the disease incidence is slightly higher in women
than in men [3].
Clinical Presentation and Natural History
Because sarcoidosis affects multiple organ systems, presentation varies
from nonspecific constitutional symptoms to those related to specific organ
involvement. Symptoms related to lung involvement (dyspnea and cough) can lead
to chest radiographs that eventually yield the diagnosis of sarcoid. One third
of patients have peripheral lymphadenopathy, most commonly involving the
cervical, axillary, and inguinal lymph nodes. One quarter of patients show
characteristic skin lesions, including erythema nodosum and lupus pernio
[3].
The natural history of sarcoidosis varies significantly from patient to
patient. The disease spontaneously remits in up to one third of patients, but
is chronic and progressive in up to 30%. There is a 1–5% fatality rate
from the disease, most commonly resulting from severe respiratory or cardiac
involvement [3].
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Fig. 2 —Pulmonary nodules in peribronchovascular distribution in
44-year-old woman with sarcoidosis. High-resolution chest CT image shows
multiple tiny pulmonary nodules centered in peribronchovascular distribution
(upper arrow). Small pulmonary nodules can also be seen lining right
major fissure (lower arrow).
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Fig. 4 —Lambda ( ) sign on 67Ga scan in 26-year-old
man with biopsy-proven sarcoidosis. Anterior image of chest shows increased
tracer uptake in right paratracheal and bilateral hilar lymph nodes, in
configuration known as "lambda sign."
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Classic Imaging Features of Sarcoidosis
Radiography
Chest radiographic features include mediastinal and bilateral hilar
lymphadenopathy, parenchymal opacities, and, in more advanced cases,
parenchymal fibrosis. A clinical staging system based on the chest radiograph
has been devised to monitor disease in patients with sarcoidosis as well as to
predict patient prognosis. The five-part staging system ranges from stage 0
(no radiographic abnormality) to stage 4 (pulmonary fibrosis), with varying
degrees of lymphadenopathy and pulmonary parenchymal abnormalities in between.
Spontaneous remission is more commonly seen in patients with stage 1 disease
(Fig. 1) than in patients with
more advanced stages [3].
MDCT
Lymphadenopathy and parenchymal involvement in the neck and chest are more
readily shown on MDCT. In the neck, palpable cervical lymphadenopathy is
identified in one third of patients, usually in the posterior triangle. In the
chest, paratracheal, mediastinal, and bilateral hilar lymphadenopathy are most
commonly identified. Characteristic parenchymal lesions include pulmonary
nodules, typically in a peribronchovascular distribution or along fissures
[2]
(Fig. 2). Less commonly,
alveolar consolidation can be seen with air bronchograms, cavitation, and
fibrosis [4].
In the abdomen, lesions are less characteristic, mimicking systemic
diseases such as lymphoma, diffuse metastatic disease, or granulomatous or
mycobacterial infection. In addition to diffuse lymphadenopathy
(Fig. 3), nonspecific
parenchymal lesions have been described, usually in the spleen and liver
[4]. Diffuse hepatic
involvement can progress in some cases to confluent hepatic fibrosis
[2].
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Fig. 5 —Palpable submental lymph node with FDG uptake in 56-year-old
woman with palpable submental lymph node. Axial fused contrast-enhanced PET/CT
image shows enlarged left submental lymph node (arrow) with increased
FDG uptake. Lesion was biopsied and was consistent with sarcoidosis.
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Gallium-67 Scanning
Gallium-67 imaging has been widely used in the diagnosis of sarcoidosis.
Gallium-67 is taken up in lesions with increased blood flow, typically in
lesions having an inflammatory or infectious cause. In sarcoidosis, a
characteristic pattern of uptake in the chest has been described as the
"lambda sign:" paratracheal and bilateral hilar uptake
[5]
(Fig. 4). Another pattern of
uptake is called the "panda sign," caused by uptake in the
lacrimal and parotid glands. Although this pattern can be seen in other
entities, such as lymphoma and HIV, the bilateral symmetric involvement of the
glands is more typical of sarcoidosis
[6]. Additionally, when the
panda sign is seen in conjunction with the lambda sign, it is highly specific
for sarcoidosis [5].
FDG PET and PET/CT
FDG PET is an important clinical tool in the evaluation of known or
suspected malignancy. Uptake of the tracer is nonspecific, however, and is
related to tissue metabolism. Thus, the agent is also readily taken up in some
infectious and inflammatory conditions. Prior studies show increased FDG
uptake in active sarcoidosis
[7,
8]. FDG uptake in sarcoidosis
is nonspecific in both intensity and pattern, and is not generally useful in
making an initial diagnosis. Additionally, marked FDG uptake in lymph nodes
and parenchymal organs can be an important mimic of malignancy, specifically
lymphoma and diffuse metastatic disease. Despite this, FDG uptake can decrease
when sarcoidosis is treated, and PET can be useful in monitoring the
effectiveness of therapy [8,
9].
Although FDG uptake is nonspecific in sarcoidosis, combining the imaging
features of sarcoidosis on CT with uptake on PET can make combined FDG PET/CT
a useful technique in monitoring disease progression or remission.
Additionally, if characteristic patterns of chest CT lesions are identified
(as described previously), along with typical patterns of lymphadenopathy, the
disease can be suggested on the basis of FDG PET/CT findings. Histologic
proof, however, often is still required because of the importance of excluding
malignancies, particularly lymphoma
[10].
Clinical Examples on FDG PET and PET/CT
Head and Neck
Head and neck involvement by sarcoidosis is usually identified as cervical
lymphadenopathy, seen in approximately one third of patients
[2]. On FDG PET, increased
uptake has been described in these lymph nodes
(Fig. 5), as well as in the
parotid glands, in a similar distribution to that seen with 67Ga
scanning [7].
Chest
Although the radiographic and CT features of sarcoidosis have been well
described in the chest, few articles have specifically addressed patterns of
FDG uptake in the lungs. Mediastinal and hilar lymphadenopathy from
sarcoidosis shows increased FDG uptake, as in other parts of the body (Fig.
6A,
6B,
6C). Lung parenchymal
involvement and FDG uptake is less well described; however, it has been shown
that FDG PET can detect lung involvement by sarcoidosis in patients after
transplantation [9].
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Fig. 6A —Confluent parenchymal lung nodules and mediastinal and
bilateral hilar lymphadenopathy with increased FDG uptake in 56-year-old woman
with biopsy-proven sarcoidosis. Axial CT image (A) shows confluent
parenchymal lung nodules (yellow arrows) and mediastinal and
bilateral hilar lymphadenopathy (blue arrows). These abnormalities
show increased FDG uptake on fused PET/CT (B) and unfused PET
(C) images.
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Fig. 6B —Confluent parenchymal lung nodules and mediastinal and
bilateral hilar lymphadenopathy with increased FDG uptake in 56-year-old woman
with biopsy-proven sarcoidosis. Axial CT image (A) shows confluent
parenchymal lung nodules (yellow arrows) and mediastinal and
bilateral hilar lymphadenopathy (blue arrows). These abnormalities
show increased FDG uptake on fused PET/CT (B) and unfused PET
(C) images.
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Fig. 6C —Confluent parenchymal lung nodules and mediastinal and
bilateral hilar lymphadenopathy with increased FDG uptake in 56-year-old woman
with biopsy-proven sarcoidosis. Axial CT image (A) shows confluent
parenchymal lung nodules (yellow arrows) and mediastinal and
bilateral hilar lymphadenopathy (blue arrows). These abnormalities
show increased FDG uptake on fused PET/CT (B) and unfused PET
(C) images.
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Abdomen
Again, as elsewhere in the body, abdominal lymph nodes secondary to
sarcoidosis can show increased FDG activity
[7]. Parenchymal lesions in the
abdomen have also been described as showing increased FDG uptake. For example,
sarcoidosis is known to cause splenomegaly and low-density focal lesions in
the spleen that have been reported to have increased FDG uptake on PET
[11] (Fig.
7A,
7B,
7C).
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Fig. 7A —Splenic lesions with uptake from sarcoidosis in 43-year-old
woman with history of Hodgkin's lymphoma. Images from combined PET/CT show
low-density lesions (arrows, A and C) in spleen on
coronal CT image (A). Lesions show increased FDG uptake on fused PET/CT
(B) and unfused PET (C) images. Because of patient's history of
lymphoma, she underwent splenectomy to assess cause of lesion, and pathology
revealed noncaseating granulomas consistent with sarcoidosis. Sarcoidosis is
known to cause splenomegaly and low-density focal lesions in the spleen and
has been reported to have increased FDG uptake on PET scans
[11].
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Fig. 7B —Splenic lesions with uptake from sarcoidosis in 43-year-old
woman with history of Hodgkin's lymphoma. Images from combined PET/CT show
low-density lesions (arrows, A and C) in spleen on
coronal CT image (A). Lesions show increased FDG uptake on fused PET/CT
(B) and unfused PET (C) images. Because of patient's history of
lymphoma, she underwent splenectomy to assess cause of lesion, and pathology
revealed noncaseating granulomas consistent with sarcoidosis. Sarcoidosis is
known to cause splenomegaly and low-density focal lesions in the spleen and
has been reported to have increased FDG uptake on PET scans
[11].
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Fig. 7C —Splenic lesions with uptake from sarcoidosis in 43-year-old
woman with history of Hodgkin's lymphoma. Images from combined PET/CT show
low-density lesions (arrows, A and C) in spleen on
coronal CT image (A). Lesions show increased FDG uptake on fused PET/CT
(B) and unfused PET (C) images. Because of patient's history of
lymphoma, she underwent splenectomy to assess cause of lesion, and pathology
revealed noncaseating granulomas consistent with sarcoidosis. Sarcoidosis is
known to cause splenomegaly and low-density focal lesions in the spleen and
has been reported to have increased FDG uptake on PET scans
[11].
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Musculoskeletal
Bone involvement in sarcoidosis can be seen in up to one third of patients,
usually in the hands and feet. Less commonly, axial skeletal involvement can
be seen. In both cases, lesions of sarcoid can be either osteolytic or
osteosclerotic, and their nonspecific appearance can make diagnosis difficult.
Increased activity can be seen on bone scintigraphy. Additionally, case
reports have described increased FDG uptake in skeletal sarcoidosis (Fig.
8A,
8B,
8C). In conjunction with the
more characteristic findings of sarcoidosis, such as mediastinal
lymphadenopathy, bone involvement from sarcoid can be suggested in patients
with increased focal bone FDG uptake rather than diffuse metastatic disease
[12,
13].
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Fig. 8A —Skeletal uptake in 56-year-old woman with known sarcoidosis
in neck, who presented with pelvic bone pain. Images from combined PET/CT scan
show multiple subtle sclerotic lesions (arrows) in bilateral iliac
bones on axial CT image (A). These lesions show increased FDG uptake on
fused PET/CT (B) and unfused PET (C) images. Biopsy of left
iliac bone lesion was consistent with sarcoidosis.
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Fig. 8B —Skeletal uptake in 56-year-old woman with known sarcoidosis
in neck, who presented with pelvic bone pain. Images from combined PET/CT scan
show multiple subtle sclerotic lesions (arrows) in bilateral iliac
bones on axial CT image (A). These lesions show increased FDG uptake on
fused PET/CT (B) and unfused PET (C) images. Biopsy of left
iliac bone lesion was consistent with sarcoidosis.
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Fig. 8C —Skeletal uptake in 56-year-old woman with known sarcoidosis
in neck, who presented with pelvic bone pain. Images from combined PET/CT scan
show multiple subtle sclerotic lesions (arrows) in bilateral iliac
bones on axial CT image (A). These lesions show increased FDG uptake on
fused PET/CT (B) and unfused PET (C) images. Biopsy of left
iliac bone lesion was consistent with sarcoidosis.
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Fig. 9 —Follicular lymphoma and asymptomatic pulmonary sarcoidosis in
44-year-old woman with history of grade 3 follicular lymphoma that is now in
remission. Patient underwent transbronchial biopsy to evaluate small lymph
nodes in chest, which revealed noncaseating granulomas consistent with
sarcoidosis. Whole-body PET image shows marked FDG uptake in bilateral axillae
and left paratracheal regions (upper arrows), as well as in abdomen
(lower arrows). Distribution of adenopathy is more consistent with
lymphoma than with sarcoidosis, especially because of lack of significant
hilar or mediastinal lymphadenopathy. Biopsy of left axillary lymph node
revealed follicular lymphoma.
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Sarcoidosis as a Mimic of Malignancy
The most common radiologic finding in sarcoidosis is intrathoracic
lymphadenopathy, seen in up to 85% of patients
[2]. Abdominal lymphadenopathy
is seen 30% of cases, with massive lymphadenopathy (lymph nodes > 2 cm)
seen in 10% of patients [4].
Given the presence of lymphadenopathy in such a large percentage of patients
with sarcoidosis, it is not surprising that one of the more common
differential considerations in these patients is lymphoma. Additionally, as
described previously, musculoskeletal involvement in sarcoidosis can manifest
as increased focal uptake throughout the skeleton, which can mimic diffuse
metastatic disease [12,
13].
To further complicate matters, a known association exists between
sarcoidosis and lymphoma, described in 1986 by Brinker and called
"sarcoidosis–lymphoma syndrome"
[14]. Several cases studies
have been published describing the association of chronic active sarcoidosis
and systemic lymphoma, both Hodgkin's and non-Hodgkin's lymphoma
[15,
16]
(Fig. 9). Using data from
patients with respiratory sarcoidosis who had registered with the Danish
Institute of Clinical Epidemiology, Brinker determined that patients with
sarcoidosis are at 5.5 times increased risk of developing a
lymphoproliferative disorder as other patients in the same age group
[14].
Conclusion
The imaging features of sarcoidosis are diverse and can be shown on a
variety of imaging techniques. FDG uptake on PET in patients with sarcoidosis
is variable and can mimic malignancies such as lymphoma and diffuse metastatic
disease. It is important for radiologists and nuclear medicine physicians to
recognize the common imaging features and patterns of sarcoidosis in order to
raise the possibility in the appropriate clinical setting.
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Abstract
Introduction
