AJR 2004; 182:15-28
© American Roentgen Ray Society
Imaging Manifestations of Abdominal Sarcoidosis
David M. Warshauer1 and
Joseph K. T. Lee
1 Both authors: Department of Radiology, University of North Carolina School of
Medicine, Manning Dr., Old Clinic Bldg., Rm. 2016, Box 7510, Chapel Hill, NC
27599-7510.
Received April 14, 2003;
accepted after revision July 15, 2003.
Address correspondence to D. M. Warshauer.
Introduction
Sarcoidosis is a systemic inflammatory disease of unknown origin
characterized by the formation of noncaseating granulomas. Virtually any organ
system may be involved. Pulmonary changes are the most common manifestation,
and the accompanying radiologic findings of bilateral hilar adenopathy with or
without changes of interstitial lung disease are well known and
characteristic. Involvement of abdominal viscera is less frequent, but when it
occurs, it may mimic more common infectious or neoplastic conditions and
result in unnecessary morbidity. We review our experience with the clinical
and imaging manifestations of sarcoidosis in the abdomen.
Epidemiology, Etiology, and Pathology
Sarcoidosis occurs most commonly in the third to fifth decades of life and,
in the United States, is slightly more common in women than men
[1,
2]. Although sarcoidosis is
seen worldwide, the frequency of the disease, organ system involved, acuity of
presentation, and prognosis vary widely with geography and ethnicity. Areas
with high prevalence include the United States, particularly the southeastern
region, Sweden, Denmark, and Japan, whereas a low prevalence is noted in
Spain, China, and South America
[1]. In the United States,
blacks are more commonly affected than whites, with an age-adjusted annual
incidence rate of 35.5 per 100,000 for blacks and 10.9 per 100,000 for whites
[2]. Pulmonary complications
are the major cause of death in the United States; however, in Japan, cardiac
involvement is a more common cause of mortality
[1,
3]. Familial occurrence of the
disease has been described and is more common among blacks than whites. Human
leukocyte antigen analysis suggests a polygenic mode of risk inheritance
[1].
Although the etiology of sarcoidosis is unknown, speculation has centered
on the interaction of an unknown antigenic factor triggering an exaggerated
cellular immune response in genetically susceptible individuals. Geographic
variation in the organ system affected and the pattern of the illness suggest
that there may be multiple antigenic triggers
[1].
The presence of noncaseating granulomas is the pathologic hallmark of
sarcoidosis. Although rare, central necrosis and cavitation have been reported
in pulmonary lesions [4].
Diagnosis of sarcoidosis must be based on the entirety of the clinical
presentation because noncaseating granulomas are also found in association
with several other infectious agents (e.g., tuberculosis, histoplasmosis,
brucellosis, and toxoplasmosis), occupational and environmental exposures
(e.g., beryllium, talc, and fungi), autoimmune disorders (e.g., Wegener's
granulomatosis and primary biliary cirrhosis), and neoplasia (e.g., lymphoma
and solid tumors) [5]. This
latter association is particularly relevant when sarcoidosis produces masslike
lesions that mimic abdominal carcinomas. These granulomas, which are
morphologically identical to sarcoids, can be seen both in the tumor itself as
well as within regional nodes that may not contain tumors. Presumably the
granulomas form in response to soluble antigenic factors derived from tumor
cells eliciting an immunologic hypersensitivity reaction
[6].
Symptoms associated with sarcoidosis are both systemic (e.g., fatigue,
fever, or weight loss) and organ-specific (e.g., shortness of breath or
cough). Löfgren's syndrome refers to the association of bilateral hilar
adenopathy, fever, and erythema nodosum. Although it is commonly due to
sarcoidosis, the syndrome can have other causes. Heerfordt's syndrome of
parotid gland enlargement, fever, uveitis, and cranial nerve palsies is almost
always produced by sarcoidosis, as is lupus pernio (indurated plaques on the
cheeks, lips, nose, and ears) associated with pulmonary infiltrates and lytic
lesions that affect the small bones of the hands and feet
[7]. However, sarcoidosis
frequently produces no symptoms. Estimates from autopsy research suggest that
the number of cases of sarcoidosis may be 10 times more than the number of
cases that are clinically apparent
[8]. In a Japanese autopsy
study, more than half of the individuals with sarcoidosis had not received a
clinical diagnosis before death
[3].
Abdominal Manifestations
Abdominal viscera are frequently involved in sarcoidosis, although this
involvement usually does not produce symptoms. The liver and spleen are the
most frequently involved viscera, with granulomata noted in 40–60% of
patients in two autopsy series
[3,
9]. Renal involvement is seen
in 8–19% of patients. At autopsy, pancreatic, intestinal, and testicular
sarcoidosis have been found in 5% or less of patients
[3,
9]. In the following sections,
we review in detail the reported appearance of abdominal sarcoidosis.
Liver
Liver involvement in sarcoidosis can be documented at biopsy in
24–94% of patients [10,
11]. Laboratory evidence of
liver dysfunction is seen in 2–60% of patients, with the alkaline
phosphatase level being most commonly affected. Despite these incidences,
symptomatic liver disease occurs in less than 5% of patients with sarcoidosis.
Portal hypertension and cirrhosis are rare
[7].
The most common radiographic finding of hepatic sarcoidosis is
hepatomegaly. In a review of 59 patients with sarcoidosis at our institution,
we found that 29% of the patients had a liver span greater than 20 cm on CT,
and 8% of the 59 exhibited marked hepatomegaly (liver span > 25 cm)
[12]. Other studies on
sarcoidosis have found similar results
[13,
14], although in one study,
only 4% of patients had enlarged livers for unknown reasons
[15]. In most patients, the
liver appears homogeneous; however, a pattern of multiple low-density
intrahepatic septa on contrast-enhanced CT has also been described
[16]. On sonography, a pattern
of either diffuse increased homogeneous or heterogeneous echogenicity has been
reported in patients with hepatic sarcoidosis
[17].
Focal nodules are also noted in the livers of patients with hepatic
sarcoidosis. Pathologically, these nodules are thought to represent the
coalescence of small granulomas into macroscopically visible lesions. In our
experience, these nodules are noted in 5% of patients
[12]. In other studies,
frequencies of focal nodules have ranged from 0% to 19%
[13–15].
The nodules are typically innumerable and diffusely distributed. The size of
such nodules ranges from 1–2 mm to several centimeters
[18,
19]. Hepatomegaly, splenic
nodules, and adenopathy are frequently, but not invariably, associated with
the presence of liver nodules
[18]. In one study, 69% of
patients with hepatic nodules also had splenic lesions
[19]. Liver involvement by
sarcoidosis typically responds to steroids. In one case report, hepatic
nodules disappeared after 3 months of steroid therapy, although hepatomegaly
remained [20]. We have seen a
similar decrease in the size and visibility of hepatic and splenic nodules
after 5 months of steroid therapy
[18].
On contrast-enhanced CT, liver nodules appear as hypodense masses relative
to adjacent normal parenchyma. Peripheral enhancement typically is not seen
[18] (Fig.
1A,
1B,
1C,
1D). On MRI, the lesions are
hypointense on all sequences and hypoenhancing relative to the background
liver [17,
21] (Fig.
1A,
1B,
1C,
1D). Lesions are most
conspicuous on the T2-weighted fat-saturated images and the early-phase
gadolinium-enhanced T1-weighted images
[21]. The periportal increase
in signal intensity on T2-weighted images may reflect the tendency of sarcoid
granulomas to appear along the portal tracts
[17] (Fig.
2A,
2B,
2C,
2D). On sonography, nodules
have been reported to be hypoechoic relative to the background liver
[17], although we have also
seen nodules that are hyperechoic (Figs.
3A,
3B and
4). The difference may depend
on the echogenicity of the liver or the degree of fibrosis present in the
granuloma. Although calcification is uncommon, we have seen it in a patient
with long-standing disease.
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Fig. 1A. —29-year-old man with pulmonary sarcoidosis who presented with
malaise, anorexia, and abdominal discomfort. Liver biopsy showed noncaseating
granulomata consistent with sarcoidosis. (Reprinted with permission from
[21]) Contrast-enhanced CT
scan shows hepatomegaly with innumerable small hypodense hepatic nodules.
Portal adenopathy (arrows) is also present.
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Fig. 1B. —29-year-old man with pulmonary sarcoidosis who presented with
malaise, anorexia, and abdominal discomfort. Liver biopsy showed noncaseating
granulomata consistent with sarcoidosis. (Reprinted with permission from
[21]) T2-weighted
fat-saturated image (B), T1-weighted fast low-angle shot image
(C), and early-phase gadolinium-enhanced T1-weighted fast low-angle
shot image (D) depict innumerable hypointense hepatic nodules. Nodules
are most clearly seen on T2-weighted and gadolinium-enhanced images. Portal
adenopathy (arrows) shows increased signal intensity on T2-weighted
image, decreased signal intensity on T1-weighted images, and enhancement on
gadolinium-enhanced T1-weighted images.
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Fig. 1C. —29-year-old man with pulmonary sarcoidosis who presented with
malaise, anorexia, and abdominal discomfort. Liver biopsy showed noncaseating
granulomata consistent with sarcoidosis. (Reprinted with permission from
[21]) T2-weighted
fat-saturated image (B), T1-weighted fast low-angle shot image
(C), and early-phase gadolinium-enhanced T1-weighted fast low-angle
shot image (D) depict innumerable hypointense hepatic nodules. Nodules
are most clearly seen on T2-weighted and gadolinium-enhanced images. Portal
adenopathy (arrows) shows increased signal intensity on T2-weighted
image, decreased signal intensity on T1-weighted images, and enhancement on
gadolinium-enhanced T1-weighted images.
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Fig. 1D. —29-year-old man with pulmonary sarcoidosis who presented with
malaise, anorexia, and abdominal discomfort. Liver biopsy showed noncaseating
granulomata consistent with sarcoidosis. (Reprinted with permission from
[21]) T2-weighted
fat-saturated image (B), T1-weighted fast low-angle shot image
(C), and early-phase gadolinium-enhanced T1-weighted fast low-angle
shot image (D) depict innumerable hypointense hepatic nodules. Nodules
are most clearly seen on T2-weighted and gadolinium-enhanced images. Portal
adenopathy (arrows) shows increased signal intensity on T2-weighted
image, decreased signal intensity on T1-weighted images, and enhancement on
gadolinium-enhanced T1-weighted images.
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Fig. 2B. —64-year-old woman with hepatosplenic sarcoidosis. (Reprinted
with permission from [21])
T2-weighted fat-saturated image shows multiple small hypointense nodules in
spleen and less conspicuous lesions in liver. Central periportal high signal
intensity (arrows) is seen.
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Fig. 3A. —31-year-old woman with sarcoidosis. (Courtesy of Chong W,
Chapel Hill, NC) Contrast-enhanced CT scan shows multiple hypodense hepatic
nodules. Portal adenopathy (arrow) is also noted.
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Fig. 4. —39-year-old woman with fatigue and elevated alkaline
phosphatase level. Sonogram of liver shows diffuse inhomogeneous echotexture
with areas of increased echogenicity (arrows) of varying sizes. Liver
and cervical lymph node biopsies showed granulomatous inflammation consistent
with sarcoidosis. (Courtesy of Mittelstaedt C, Chapel Hill, NC)
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Biliary Tree
Sarcoidosis can involve the intra- or extra-hepatic biliary tree.
Intrahepatic involvement typically occurs with granulomatous involvement of
the portal triads, producing a cholestatic picture. Although this appearance
may mimic that of primary biliary cirrhosis, the absence of antimitochondrial
antibodies in sarcoidosis is a distinguishing feature
[22]. Involvement of the
extrahepatic ducts can produce strictures that mimic cholangiocarcinoma
[23]. Enlarged portal nodes
may also sufficiently compress the biliary tree to produce obstructive
jaundice [24] (Fig.
5A,
5B,
5C). Resolution with steroids
has been described in several case reports
[25].
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Fig. 5B. —56-year-old woman with jaundice. (Courtesy of Nelson RC,
Durham, NC) Contrast-enhanced CT scans (C obtained 5 mm caudad to
B) shows intrahepatic bile duct dilatation with multiple enlarged
portal and celiac lymph nodes (arrows). Fine-needle aspiration of
porta hepatis nodes revealed noncaseating granulomas consistent with
sarcoidosis. Biliary stent is indicated by arrowhead.
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Fig. 5C. —56-year-old woman with jaundice. (Courtesy of Nelson RC,
Durham, NC) Contrast-enhanced CT scans (C obtained 5 mm caudad to
B) shows intrahepatic bile duct dilatation with multiple enlarged
portal and celiac lymph nodes (arrows). Fine-needle aspiration of
porta hepatis nodes revealed noncaseating granulomas consistent with
sarcoidosis. Biliary stent is indicated by arrowhead.
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Spleen
Fine-needle aspiration biopsy of the spleen has revealed granulomas in
24–59% of patients with sarcoidosis
[26,
27]. Autopsy studies have
similarly shown involvement in 38–77% of patients with the disease
[7]. Although symptoms
referable to the spleen itself are unusual, systemic complaints of fever,
malaise, and weight loss are common, particularly in patients with
splenomegaly [12]. In our
experience, splenomegaly (greatest splenic dimension 
14 cm) is seen in
about a third of patients with sarcoidosis; marked splenomegaly (greatest
splenic dimension 18 cm) is present in 6% of patients
[12]. Other studies have
reported finding splenomegaly in 25–60% of patients
[13–15].
At our institution, hypodense splenic nodules are seen in approximately 15%
of patients with sarcoidosis
[12]. Other studies have shown
both lower (6%) [15] and
higher (33%) [14] values, a
variation that is probably linked to geographic and ethnic differences in
study populations. Lesions are usually diffusely distributed and innumerable.
Most nodules are between 0.1 and 3.0 cm, with a mean of approximately 1.0 cm
[18,
19]. Isolated or predominant
involvement of the spleen by nodules is more common than isolated or
predominant hepatic nodular disease
[18,
19]. Splenomegaly is common,
although 17% of patients with nodules at our institution were found to have
normal-size spleens [18]. Of
our patients with hepatosplenic nodules, 76% also had concomitant abdominal
lymphadenopathy [18]. Punctate
calcifications are relatively uncommon in our experience but have been
reported as affecting 16% of patients in one study
[15].
The occurrence of nodular hepatosplenic sarcoid is more common during the
first 5 years of sarcoidosis, with only six of 32 patients in one series
having had the disease longer at the time that nodular hepatosplenic sarcoid
was diagnosed [18]. Abdominal
or systemic symptoms were also seen frequently in patients with nodular
hepatosplenic sarcoidosis. In one study, they were present in 66% of the
patients [18].
On contrast-enhanced CT, the splenic nodules are hypodense relative to
adjacent normal spleen. Peripheral enhancement is not seen (Figs.
2A,
2B,
2C,
2D,
6A,
6B,
6C,
6D, and
7A,
7B). On MRI, the lesions are
also hypointense on all sequences and hypoenhancing, although they become less
conspicuous on delayed imaging, suggesting equilibration
[21] (Figs.
2A,
2B,
2C,
2D and
8A,
8B,
8C). Lesions are best seen on
early-phase gadolinium-enhanced T2-weighted fat-suppressed or T1-weighted
images [21]. Data on the
typical sonographic appearance are limited. In one report, lesions visible on
contrast-enhanced CT were not seen on sonography, suggesting that the acoustic
impedance of the granulomas was similar to that of normal splenic tissue
[28]. We have noted that
splenic nodules resulting from sarcoidosis show a slightly hyperechoic or
inhomogeneous appearance (Figs.
6A,
6B,
6C,
6D and
8A,
8B,
8C), although hypoechoic
nodules have also been reported
[17].
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Fig. 6A. —52-year-old woman with leukopenia and mild anemia. (Reprinted
with permission from [12])
Contrast-enhanced CT scan shows mild splenomegaly with multiple small
hypoattenuating nodules scattered diffusely throughout spleen.
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Fig. 6C. —52-year-old woman with leukopenia and mild anemia. (Reprinted
with permission from [12])
Photograph of gross specimen of spleen obtained at splenectomy shows multiple
macroscopic nodules separated by thin bands of splenic parenchyma
(arrow indicates one of many nodules).
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Fig. 6D. —52-year-old woman with leukopenia and mild anemia. (Reprinted
with permission from [12])
Photomicrograph of histopathologic specimen reveals multiple small granulomas
(arrows) that have coalesced to form macroscopic nodules (N). (H and
E, x10)
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Fig. 7A. —21-year-old woman with fatigue and elevated
angiotensin-converting enzyme level. Contrast-enhanced CT scan shows multiple
well-defined hypodense nodules scattered throughout spleen. Smaller and less
well-defined hepatic nodules are observed, along with portal adenopathy
(arrow).
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Fig. 7B. —21-year-old woman with fatigue and elevated
angiotensin-converting enzyme level. Photograph obtained at laparoscopy
reveals white plaques studding liver, presumably corresponding to sarcoid
granulomas.
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Fig. 8A. —42-year-old woman with sarcoidosis. (Courtesy of Mittelstaedt
C, Chapel Hill, NC) T2-weighted fat-saturated image (A) and
gadolinium-enhanced T1-weighted image (B) reveal splenomegaly with
hypointense and hypoenhancing splenic nodules.
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Fig. 8B. —42-year-old woman with sarcoidosis. (Courtesy of Mittelstaedt
C, Chapel Hill, NC) T2-weighted fat-saturated image (A) and
gadolinium-enhanced T1-weighted image (B) reveal splenomegaly with
hypointense and hypoenhancing splenic nodules.
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Abdominal Lymph Nodes
In our experience, abdominal adenopathy— defined as two or more nodes
with a short axis greater than 1 cm or nodes in the retrocrural area with a
short axis greater than 6 mm—is seen in approximately 30% of patients
with sarcoidosis. Extensive adenopathy (node size > 2 cm and involvement of
four or more sites) is found in approximately 10% of patients
[12]. Other studies have shown
similar or higher frequencies
[14,
15]. In a study of 11 patients
with abdominal or pelvic adenopathy from sarcoidosis, enlarged celiac artery
nodes were seen in 82%; porta hepatis nodes, in 73%; paraaortic or paracaval
nodes, in 73%; gastrohepatic ligament nodes, in 55%; mesenteric nodes, in 55%;
superior mesenteric artery nodes, in 45%; and pelvic nodes, in 33%.
Retrocrural nodes were involved in only 18% of the patients. In comparing the
group of patients with sarcoidosis with a group of patients with non-Hodgkin's
lymphoma, retrocrural nodes were involved significantly more frequently (70%)
in the patients with lymphoma. No significant difference in the frequency of
involvement at other nodal stations was found between the patients with
lymphoma and the patients with sarcoidosis. Paraaortic and pelvic involvement
was more commonly found in the lymphoma group; however, this difference
between the two groups did not reach statistical significance in this
relatively small series [14].
Mean node size was also significantly smaller in patients with sarcoidosis
than in patients with lymphoma (mean ± SD, 2.6 ± 1.7 cm in
sarcoidosis vs 8.0 ± 5.5 cm in lymphoma), but diameters of some nodes
in patients with sarcoidosis were as large as 7.5 cm
[14]. Confluent masses were
also significantly less common in patients with sarcoidosis than in patients
with lymphoma. In one series, masses were seen in only 9% of the patients with
sarcoidosis but were seen in 50% of the patients with lymphoma
[14].
Nodal calcification is unusual in sarcoidosis. Enlarged abdominal lymph
nodes may be the only abnormal finding on an imaging study, as was the case in
approximately 50% of patients in one series
[15]. Patients with
lymphadenopathy tend to be younger (mean age in patients with adenopathy, 33
years; mean age in patients without lymphadenopathy, 43 years)
[12] and are more likely to
have symptoms than those without lymphadenopathy, although such symptoms may
consist only of systemic distress such as fever, malaise, and weight loss.
Nodal enlargement producing obstruction of adjacent structures has, however,
been observed in the biliary tree and ureter. In one case report, a
27-year-old man with a known diagnosis of sarcoidosis presented with both
jaundice and hydronephrosis from nodal compression. Resolution was observed
after steroid therapy [29].
Chylous ascites has also been reported in one patient with extensive
mesenteric and paraaortic adenopathy
[30]. This patient did not
respond to steroids, suggesting that fibrosis may have been present. One case
of venous insufficiency in the small intestine resulting from sarcoid nodes
compressing the mesenteric vein has also been described
[31].
On CT, the nodes affected by sarcoidosis generally show homogeneous
soft-tissue attenuation (Figs.
1A,
1B,
1C,
1D,
3A,
3B,
7A,
7B, and
9A,
9B). On MRI, these nodes
appear hyperintense on T2-weighted fat-saturated images and show mild
enhancement on gadolinium-enhanced images
[21] (Fig.
1A,
1B,
1C,
1D). A fine hypointense
speckled appearance of the nodes on T2-weighted fat-saturated images has been
described, presumably reflecting macroscopic aggregation of granulomas
[21] (Fig.
9A,
9B). Other authors have
reported either homogeneously increased T2 signal in the nodes or a central
low signal surrounded by peripheral high signal on T2-weighted imaging
[32]. On sonography, nodes
have been described as containing low-level echoes and increased through
transmission, mimicking lymphoma
[32]. Massive echolucent
retrocardiac nodes resulting from sarcoidosis may simulate cor triatriatum
[33]. We have seen a more
nondescript appearance with a slightly hypoechoic echotexture compared with
the liver (Fig. 10).
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Fig. 9A. —34-year-old woman with sarcoidosis who presented with
malaise, anorexia, weight loss, fever, and night sweats. (Reprinted with
permission from [21])
Contrast-enhanced axial CT scan shows marked splenomegaly with gastric
compression and extensive upper abdominal adenopathy (arrows).
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Fig. 9B. —34-year-old woman with sarcoidosis who presented with
malaise, anorexia, weight loss, fever, and night sweats. (Reprinted with
permission from [21])
T2-weighted fat-saturated image reveals hyperintense lymphadenopathy
(arrows), with suggestion of hypointense speckling.
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Fig. 10. —42-year-old man with uveitis, bilateral hilar adenopathy, and
pulmonary interstitial opacities. Sonogram shows enlarged slightly hypoechoic
celiac lymphadenopathy (n), liver (L), and celiac axis (arrow).
Biopsy of subcutaneous nodule revealed noncaseating granulomata consistent
with sarcoidosis. (Courtesy of Mittelstaedt C, Chapel Hill, NC)
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Pancreas
Sarcoid involvement of the pancreas is uncommon. Results of autopsy studies
have suggested an incidence of 1%, although in one series, mild elevation in
pancreatic amylase level was noted in 9% of patients
[34,
35]. Clinically evident
disease is rare and usually results from either direct infiltration of the
gland or compression of pancreatic structures by enlarged peripancreatic
nodes. Abdominal and back pain, weight loss, anorexia, jaundice, and pruritus
are all reported and usually result from obstruction of the bile or pancreatic
duct. Pancreatitis without an obstructive mass has also been reported and may
result from direct gland involvement
[36]. Sarcoid-associated
hypercalcemia also may induce acute pancreatitis. Because prolonged sun
exposure in patients with sarcoidosis may result in acute hypercalcemia, an
episode of pancreatitis may be the initial presentation of sarcoidosis in
patients on vacation in sunny climates
[37]. Diabetes due to gland
infiltration or pancreatitis also has been reported
[38,
39].
The imaging manifestations of pancreatitis resulting from sarcoidosis are
indistinguishable from those of pancreatitis caused by other conditions.
Pancreatic mass lesions associated with sarcoidosis are rare but may mimic
pancreatic adenocarcinomas in both their presentation and appearance. Lesions
as large as 6–7 cm have been described
[36,
40]. Associated narrowing or
obstruction of the common bile duct as well as the portal and splenic veins
also has been observed [41,
42]. Concomitant enlargement
of peripancreatic nodes may be seen
[40]. Typical lesions have
been described as hypodense and hypo- or nonenhancing on CT
[40,
43]. On sonography, the masses
are hypoechoic [40].
Cholangiograms typically show a long, smoothly tapered narrowing rather than
the more abrupt termination associated with tumor
[43].
Percutaneous biopsy may be helpful in arriving at a diagnosis in cases of a
pancreatic mass resulting from sarcoid, but it should be noted that
sarcoidlike changes are occasionally seen in association with pancreatic
neoplasms as well as with other tumors, both in the primary tumor and in
regional nodes that may or may not contain tumor. This condition has been
reported in approximately 4% of patients with carcinomas in various sites and
7% of patients with non-Hodgkin's lymphoma
[6]. Most patients with
pancreatic sarcoidosis respond to corticosteroids, so resection should be
avoided if possible [43].
Luminal Gastrointestinal Tract
The most common site of sarcoid involvement in the gastrointestinal tract
is the stomach, although reported locations range from the esophagus to the
rectum. Symptomatic involvement of the luminal gastrointestinal tract by
sarcoidosis is estimated to occur in less than 1% of patients
[34]. Asymptomatic involvement
may be more frequent. In a study of 60 asymptomatic patients with sarcoidosis,
10% were found to have gastric mucosal granulomas
[44]. More extensive disease
may result in abdominal pain, obstruction, bleeding, and malabsorption.
Lesions typically respond to steroids
[45–47],
although in some reported cases, the abnormal morphology remained, suggesting
that fibrosis may persist after resolution of the granulomatous inflammation
[46,
48].
Lesions in the gastrointestinal tract show a varied appearance. Plaquelike
lesions have been reported in the esophagus
[45]. Gastric sarcoidosis may
present as mucosal nodularity and thickened irregular folds, radiographic
features that may be indistinguishable from those of Ménétrier's
disease [45,
49]
(Fig. 11). Apthous ulcers and
larger ulcerations have been seen as well as linear and polypoid filling
defects in the stomach [49]
(Fig. 12A,
12B,
12C). A linitis
plastica–type appearance has been identified and can mimic involvement
by gastric adenocarcinomas
[50] (Fig.
13A,
13B). In the small bowel, a
circumferential obstructive process due to sarcoidosis also has been described
in the duodenum [48,
51]. Colonic sarcoidosis may
appear as irregular mass lesions mimicking carcinoma
[52–54]
(Fig. 14A,
14B,
14C,
14D). Sarcoidosis in the
appendix may produce appendicitis
[51].
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Fig. 11. —24-year-old man with epigastric pain and hematemesis. Spot
image from upper gastrointestinal examination shows thickened gastric folds.
Gastric biopsy revealed noncaseating granulomata consistent with sarcoidosis.
(Courtesy of Levy A, Armed Forces Institute of Pathology, Washington, DC)
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Fig. 12A. —36-year-old woman with nausea and vomiting. Radiograph
obtained at upper gastrointestinal examination shows irregular gastric
ulceration (U) with deformity and narrowing of gastric body and antrum
(arrows).
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Fig. 12B. —36-year-old woman with nausea and vomiting. Contrast-enhanced
CT scan obtained through upper abdomen shows thickening of gastric antrum and
body (arrows) with paraaortic adenopathy (arrowhead).
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Fig. 12C. —36-year-old woman with nausea and vomiting. Contrast-enhanced
CT scan obtained through lower abdomen shows mesenteric adenopathy
(arrows) with thickening of cecum and terminal ileum
(arrowhead). Because ulcerations proved refractory to therapy,
antrectomy and Billroth's I anastomosis were performed along with ileocecal
resection and liver biopsy. Histologic examination of pathology specimens
showed granulomatous inflammation consistent with sarcoidosis.
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Fig. 13A. —21-year-old woman with nausea, vomiting, and weight loss.
Radiograph obtained at upper gastrointestinal examination shows antral
narrowing and deformity. Biopsy revealed noncaseating granulomata.
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Fig. 14A. —43-year-old man with right lower quadrant pain and weight
loss. Compression spot film image obtained during barium enema shows irregular
narrowing of cecal lumen. (Reprinted with permission from
[54])
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Fig. 14B. —43-year-old man with right lower quadrant pain and weight
loss. Contrast-enhanced CT scan shows circumferentially thickened cecum.
(Courtesy of Levy A, Armed Forces Institute of Pathology, Washington, DC)
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Fig. 14C. —43-year-old man with right lower quadrant pain and weight
loss. Abdominal sonogram also shows thickened cecum. At exploratory
laparotomy, large cecal mass with extension into small bowel was noted with
accompanying adenopathy. Right hemicolectomy was performed. Pathology showed
noncaseating granulomatous inflammation involving ileum, colon, and lymph
nodes, consistent with sarcoidosis. (Courtesy of Levy A, Armed Forces
Institute of Pathology, Washington, DC)
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Fig. 14D. —43-year-old man with right lower quadrant pain and weight
loss. Photomicrograph of histopathologic specimen obtained from cecum shows
chronic inflammatory changes in mucosa and noncaseating submucosal granulomas
(arrows). (H and E, x10) (Reprinted with permission from
[54])
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Exclusion of other causes of granulomatous inflammation, including fungal
and mycobacterial diseases and Crohn's disease, is important. The appearance
of pathologic specimens may offer some features with which to distinguish
sarcoidosis from other entities. Sarcoidosis is frequently limited to the
mucosa, whereas Crohn's disease is a transmural process
[51]. Sarcoidosis is often
accompanied by an elevated serum angiotensin-converting enzyme (ACE) level;
unlike Crohns's disease, it responds rapidly to steroids. Concurrent
involvement of other organ systems by sarcoidosis may also be helpful in
determining the correct diagnosis.
Genitourinary Tract
Granulomatous involvement of the kidney has been reported in 7–22% of
patients with sarcoidosis at autopsy
[7]. Nephrotic syndrome,
glomerulonephritis, and tubulointerstitial disease all have been reported but
are rare. Nephromegaly or renal atrophy may result, depending on the extent
and duration of involvement. Radiographically detectable renal masses are
unusual [55]. Multiple 2- to
3-cm isodense masses that enhance less than the adjacent normal renal
parenchyma have been reported in a patient with nodular involvement of the
liver and spleen [56]. The
renal deposits may mimic the appearance of lymphoma or metastasis (Figs.
15 and
16A,
16B).
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Fig. 15. —34-year-old man with bilateral hypoenhancing renal masses
(arrows). Fine-needle aspiration of left kidney showed findings
compatible with sarcoidosis. (Courtesy of Levy A, Armed Forces Institute of
Pathology, Washington, DC)
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Fig. 16A. —35-year-old woman with abdominal pain. (Courtesy of Levy A,
Armed Forces Institute of Pathology, Washington, DC) Contrast-enhanced CT scan
shows heterogeneous mass involving left kidney with paraaortic adenopathy.
Patient underwent left nephrectomy.
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Fig. 16B. —35-year-old woman with abdominal pain. (Courtesy of Levy A,
Armed Forces Institute of Pathology, Washington, DC) Photograph of gross
specimen shows granulomatous mass. Microscopic pathologic findings were
compatible with sarcoidosis.
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Hydronephrosis may be caused by compression of the ureters by enlarged
retroperitoneal nodes. Resolution of both the nodal enlargement and the
hydronephrosis has been reported with administration of steroids
[29].
The most frequent effect of sarcoidosis in the kidney is due to
hypercalcemia or hypercalciuria. Nephrocalcinosis, nephrolithiasis, and
interstitial calcium deposition all have been reported and may lead to renal
failure. Radiographically detectable nephrocalcinosis is reported to occur in
1–4% of patients [15,
56]. Hypercalciuria is more
common, being reported in 15–62% of patients. Hypercalcemia is noted in
3–11% of patients [7].
Increased conversion of 25-hydroxyvitamin D3 to active 1,25
dihydroxyvitamin D by granuloma macrophages causes disturbance in calcium
metabolism. This overproduction then results in increased intestinal calcium
absorption [57]. Most patients
with hypercalcemia have radiographic evidence of pulmonary disease, although
this occurrence is not consistently found
[58]. Acute sunlight exposure
may precipitate hypercalcemia by increasing the availability of substrate for
this conversion. Such acute hypercalcemia may result in malaise, dehydration,
or pancreatitis and may be the initial presentation of sarcoidosis
[37].
Epididymal and testicular involvement by sarcoidosis has also been
reported. Unilateral disease is most common, but bilateral involvement is not
rare. On sonography, the resultant masses are described as homogeneously
hypoechoic [59]
(Fig. 17).
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Fig. 17. —44-year-old man with bilateral testicular pain. Testicular
sonogram reveals multiple bilateral hypoechoic masses. Excisional biopsy of
right testicular mass was performed. Gross pathologic examination (not shown)
revealed firm tan mass in wedge of testicular tissue. Microscopic examination
(not shown) found confluent epithelioid granulomas compatible with
sarcoidosis. (Courtesy of Levy A, Armed Forces Institute of Pathology,
Washington, DC)
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Abdominal Wall
Sarcoidosis can involve the skeletal muscle and produce either a nodular,
myopathic, or myositic form. Radiographic changes described with the nodular
form of sarcoidosis include nodules extending along the muscle fibers. The
atrophic myopathic form is characterized by muscular atrophy and fatty
infiltration [60]. Although
the muscle is generally smaller than normal, pseudohypertrophy from abundant
fatty infiltration has also been described. Involvement of the extremities is
most common; however, sarcoidosis involving the musculature of the abdominal
wall has been reported [61]
(Fig. 18).
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Fig. 18. —CT scan obtained in 44-year-old man who presented with firm
mass in right upper quadrant that corresponded to abnormal right rectus
abdominis muscle. Note sarcoid nodule in subcutaneous fat. Biopsy of left
internal oblique muscle showed noncaseating granulomas and increased
connective tissue and fat consistent with sarcoid myopathy and
pseudohypertrophy. (Reprinted with permission from
[61])
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Sarcoidosis also may involve the subcutaneous fat-producing nodules or a
more diffuse infiltrative lesion. Slight enhancement of the lesion relative to
the muscle is reported in the nodular form; little enhancement is seen in the
diffuse form. Both forms show signal intensity similar to that of muscle on
T1-weighted images and heterogeneously increased T2 signal
[62].
Correlation of Abdominal Sarcoidosis with Pulmonary Involvement
Involvement of the abdominal viscera frequently occurs in the context of
more extensive chest disease; however, abdominal sarcoidosis without pulmonary
or mediastinal involvement is not rare. In a study at our institution, between
25% and 38% of patients who had sarcoidosis with abdominal adenopathy,
hepatomegaly, or splenomegaly had normal findings on chest radiography
[12]. This frequency persisted
even when the abdominal findings of sarcoidosis were marked. Normal findings
on chest radiographs were noted in one of three patients whose spleen size
exceeded 18 cm, in two of five patients with marked adenopathy, and in two of
four patients whose liver span exceeded 25 cm
[12]. Similar findings have
been observed in other studies in which the authors have concluded that there
was no correlation between the degree of chest abnormality and the involvement
of liver, spleen, or node [14,
15].
The extent of pulmonary involvement has been evaluated in patients with
nodular hepatosplenic sarcoidosis both at initial presentation and on
subsequent follow-up visits. In a study of 32 patients with nodular
hepatosplenic sarcoidosis, 25% had normal chest radiographs. Sixty-one percent
of patients had stage 1 or 2 findings on chest radiographs, and 14% had stage
3 or 4 findings on chest radiographs. In the subset of patients for whom
follow-up was available, 74% had no change in stage, suggesting that the
presence of radiographically visible splenic nodules does not portend a bad
pulmonary prognosis [18]. Case
reports of sarcoid in other abdominal viscera also suggest that there is no
firm correlation between chest findings and abdominal disease
[41,
43,
46,
52,
56,
62].
ACE Level, 67Gallium (Ga) Citrate Scintigraphy, FDG Positron Emission Tomography, and Abdominal Sarcoidosis
Several markers and techniques have been investigated for assessment of
disease activity and location in sarcoidosis including serum ACE levels,
67Ga citrate scintigraphy, and FDG positron emission tomography
(PET). Serum ACE is thought to be produced by the epithelioid cells within
sarcoid granulomas. It is elevated in approximately 60% of patients with
sarcoidosis, and its level is thought to reflect whole-body granuloma mass and
disease activity [63,
64]. This supposition is
supported by several studies of abdominal sarcoidosis and ACE levels. In one
study, a linear relationship was observed between ACE level and spleen size as
well as between ACE level and the presence of adenopathy and hepatosplenic
nodules. The mean serum ACE level was noted to be 3.1 times the upper limits
of a normal level in patients with sarcoidosis who had splenic nodules,
whereas the mean ACE level was 1.3 times the normal level in patients with
sarcoidosis who had no splenic nodules
[12]. In another study of
patients with nodular hepatosplenic sarcoidosis, the ACE level was elevated in
10 of 11 patients. The single patient in this study with a normal ACE level
had been receiving 40–60 mg of prednisone, which may have suppressed the
ACE [18].
Gallium-67 citrate is a nonspecific agent taken up by activated
lymphocytes, mononuclear phagocytes, and neutrophils in the lung and other
organs. Increased pulmonary uptake is reported in more than 90% of patients
with active sarcoidosis and is thought to reflect disease activity
[65,
66]. Extrapulmonary
accumulation has also been reported in the lacrimal and parotid glands,
nasopharynx, skin, bone, muscle, and abdominal nodes. Normal intense
67Ga uptake in the liver and spleen limits assessment of these
organs [67]. Although
67Ga uptake is also seen in lymphoma and granulomatous infections,
a positive finding on a 67Ga citrate scintigraphic scan may be
helpful in selecting a site for diagnostic biopsy and in monitoring disease
activity.
Increased FDG accumulation has been reported in sarcoidosis and in
granulomatous infections. Such activity may mimic neoplastic disease,
particularly in a patient in whom sarcoidosis is asymptomatic and undiagnosed.
Increased FDG activity has also been found in extrathoracic sarcoidosis,
including the liver, spleen, abdominal and inguinal nodes, muscle, skin, and
subcutaneous tissue. Activity in these more unusual sites, particularly those
in the abdomen, may mimic lymphoma
[68].
Conclusion
Sarcoidosis has been reported in virtually every abdominal organ and
compartment; the liver, spleen, and lymph nodes are the sites most commonly
involved. Imaging findings usually consist of either homogeneous organomegaly
or nodular infiltration. These infrequently seen lesions can mimic more
serious neoplastic or infectious diseases on both radiologic and scintigraphic
studies. Sarcoidosis should be included in the abdominal differential
diagnosis in the appropriate clinical setting so that therapeutic
misadventures can be avoided.
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Introduction
Epidemiology, Etiology, and...
