AJR 2005; 184:860-867
© American Roentgen Ray Society
MRI of Adrenal and Extraadrenal Pheochromocytoma
Khaled M. Elsayes1,
Vamsidhar R. Narra1,
John R. Leyendecker2,
Isaac R. Francis3,
James S. Lewis, Jr.4 and
Jeffrey J. Brown
1 Mallinckrodt Institute of Radiology, Washington University School of Medicine,
510 S Kingshighway Blvd., St. Louis, MO 63110.
2 Department of Radiology, Wake Forest University Baptist Medical Center,
Winston-Salem, NC 27157.
3 Department of Radiology, University of Michigan, Ann Arbor, MI.
4 Department of Surgical Pathology, Washington University School of Medicine,
St. Louis, MO 63110.
Received May 13, 2004;
accepted after revision August 26, 2004.
Address correspondence to V. R. Narra
(narrav{at}mir.wustl.edu).
Introduction
Pheochromocytomas are uncommon tumors arising from pheochromocytes, the
predominant cells of adrenal medulla. These tumors also arise in the
paraganglia near the aorta and the ganglia of the sympathetic chains. The
pheochromocytes constitute the chromaffin system. Chromaffin cells are
widespread and are associated with sympathetic ganglia during fetal life. Most
chromaffin cells degenerate after birth, with the majority of residual cells
remaining in the adrenal medulla
[1]. This may explain why
approximately 90% of pheochromocytomas occur in the adrenal medulla
[1].
Epidemiology
Pheochromocytomas are most common in the fourth through sixth decades of
life. Women and men are affected with similar frequency. Pheochromocytoma has
been called the 10% tumor because approximately 10% are bilateral (Figs.
1A and
1B), 10% are malignant, 10%
occur in children, and 10% are extraadrenal. The extraadrenal lesions are also
referred to as paragangliomas
[2]. It is difficult to
differentiate benign and malignant pheochromocytomas, histologically.
Therefore, malignancy is usually established by local invasion or metastases
to nonchromaffin tissues. The most common sites of metastasis include bone,
regional lymph nodes, liver, lung, and brain (Figs.
2A and
2B). Extraadrenal
pheochromocytomas have a higher prevalence of malignancy than their adrenal
counterparts [3].
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Fig. 1A. —41-year-old woman with hypertension. Coronal HASTE (A) and
axial contrast-enhanced volumetric interpolated breath-hold examination
(B) images show bilateral adrenal masses exhibiting bright T2 signal
intensity with salt-and-pepper enhancement pattern representing bilateral
pheochromocytomas (arrows).
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Fig. 1B. —41-year-old woman with hypertension. Coronal HASTE (A) and
axial contrast-enhanced volumetric interpolated breath-hold examination
(B) images show bilateral adrenal masses exhibiting bright T2 signal
intensity with salt-and-pepper enhancement pattern representing bilateral
pheochromocytomas (arrows).
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Fig. 2A. —52-year-old man with incidentally seen, pathologically proven
metastatic deposits. Axial contrast-enhanced T1-weighted 3D volumetric
interpolated breath-hold examination image (A) and axial
inversion-recovery image (B) show enhancing liver lesion and bright T2
signal within vertebral body representing metastases from malignant
pheochromocytoma 7 years after surgical removal of tumor.
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Fig. 2B. —52-year-old man with incidentally seen, pathologically proven
metastatic deposits. Axial contrast-enhanced T1-weighted 3D volumetric
interpolated breath-hold examination image (A) and axial
inversion-recovery image (B) show enhancing liver lesion and bright T2
signal within vertebral body representing metastases from malignant
pheochromocytoma 7 years after surgical removal of tumor.
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Pathology
Pheochromocytomas are well-circumscribed homogeneous masses that vary from
pink to brown to red, depending on their vascularity. Microscopically, they
consist of well-defined nests (Zellballen) of rounded to polygonal cells with
moderately abundant granular cytoplasm and rounded to slightly spindled nuclei
with a speckled chromatin pattern. Mitoses are rare. The cell nests are
separated by vascular septa and, at their periphery, have stellate
(sustentacular) supporting cells
[4].
Locations
Pheochromocytomas arise from the adrenal medulla and the sympathetic
paraganglia. Sympathetic ganglia are found predominantly in the paraaxial
region of the trunk along the prevertebral and paravertebral sympathetic
chains and in the connective tissue in or near the walls of pelvic organs.
Most pheochromocytomas are located in the abdomen (98%), with most arising
from the adrenal gland. Extraadrenal pheochromocytomas are associated with the
celiac, superior mesenteric, and inferior mesenteric ganglia, which are
retroperitoneal in location. The organ of Zuckerkandl is the only macroscopic
extraadrenal sympathetic paraganglion, located at the origin of inferior
mesenteric artery [5] (Figs.
3A and
3B). Approximately 1% of
pheochromocytomas occur in the thorax, including paravertebral posterior
mediastinal pheochromocytomas (Fig.
4). Intrapericardial pheochromocytomas have been described as
typically located adjacent to or involving the left atrium (Figs.
5A and
5B). Sympathetic ganglia are
particularly numerous along the fibers of the inferior hypogastric plexus,
leading to and entering the urogenital organs (Figs.
6A,
6B,
6C, and
6D). Pheochromocytomas of the
female genital tract are exceptionally rare with only 10 cases reported in
detail since 1926, with three of these arising in the vagina
[6] (Figs.
7A and
7B).
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Fig. 3A. —37-year-old woman with retroperitoneal mass seen on CT scan. Axial
enhanced gradient-refocused echo T1-weighted fat-saturated (A) and
coronal T2-weighted HASTE (B) images show left paraaortic well-defined
pheochromocytoma, exhibiting intensely bright T2 signal (arrow).
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Fig. 3B. —37-year-old woman with retroperitoneal mass seen on CT scan. Axial
enhanced gradient-refocused echo T1-weighted fat-saturated (A) and
coronal T2-weighted HASTE (B) images show left paraaortic well-defined
pheochromocytoma, exhibiting intensely bright T2 signal (arrow).
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Fig. 5A. —18-year-old man with hypertension and mediastinal mass seen on
echocardiography. Contrast-enhanced sagittal T1-(A) pand axial T2
-weighted (B) images of heart show intensely enhancing, bright T2
signal mass representing intrapericardial pheochromocytoma (arrow)
adjacent to left atrium.
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Fig. 5B. —18-year-old man with hypertension and mediastinal mass seen on
echocardiography. Contrast-enhanced sagittal T1-(A) pand axial T2
-weighted (B) images of heart show intensely enhancing, bright T2
signal mass representing intrapericardial pheochromocytoma (arrow)
adjacent to left atrium.
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Fig. 6A. —42-year-old man with multiple endocrine neoplasia (MEN2).
Contrast-enhanced volumetric interpolated breath-hold examination in sagittal
(A) and axial (B) views and coronal turbo spin-echo T2-weighted
image (C) show left presacral lesion (arrow), bright on T2
with intense contrast enhancement, in this case of intrapelvic presacral
pheochromocytoma. Axial contrast-enhanced volumetric interpolated breath-hold
examination image (D) shows left adrenal mass (exhibiting
salt-and-pepper contrast-enhancement pattern), representing adrenal
pheochromocytoma (arrow).
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Fig. 6B. —42-year-old man with multiple endocrine neoplasia (MEN2).
Contrast-enhanced volumetric interpolated breath-hold examination in sagittal
(A) and axial (B) views and coronal turbo spin-echo T2-weighted
image (C) show left presacral lesion (arrow), bright on T2
with intense contrast enhancement, in this case of intrapelvic presacral
pheochromocytoma. Axial contrast-enhanced volumetric interpolated breath-hold
examination image (D) shows left adrenal mass (exhibiting
salt-and-pepper contrast-enhancement pattern), representing adrenal
pheochromocytoma (arrow).
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Fig. 6C. —42-year-old man with multiple endocrine neoplasia (MEN2).
Contrast-enhanced volumetric interpolated breath-hold examination in sagittal
(A) and axial (B) views and coronal turbo spin-echo T2-weighted
image (C) show left presacral lesion (arrow), bright on T2
with intense contrast enhancement, in this case of intrapelvic presacral
pheochromocytoma. Axial contrast-enhanced volumetric interpolated breath-hold
examination image (D) shows left adrenal mass (exhibiting
salt-and-pepper contrast-enhancement pattern), representing adrenal
pheochromocytoma (arrow).
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Fig. 6D. —42-year-old man with multiple endocrine neoplasia (MEN2).
Contrast-enhanced volumetric interpolated breath-hold examination in sagittal
(A) and axial (B) views and coronal turbo spin-echo T2-weighted
image (C) show left presacral lesion (arrow), bright on T2
with intense contrast enhancement, in this case of intrapelvic presacral
pheochromocytoma. Axial contrast-enhanced volumetric interpolated breath-hold
examination image (D) shows left adrenal mass (exhibiting
salt-and-pepper contrast-enhancement pattern), representing adrenal
pheochromocytoma (arrow).
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Fig. 7A. —37-year-old woman with postcoital headache and fainting spells.
Axial contrast-enhanced gradient-refocused echo T1-weighted fat-saturated
(A) and sagittal T2-weighted turbo spin-echo (B) images show
homogeneously enhanced and intensely bright T2 signal of vaginal
pheochromocytoma (arrow).
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Fig. 7B. —37-year-old woman with postcoital headache and fainting spells.
Axial contrast-enhanced gradient-refocused echo T1-weighted fat-saturated
(A) and sagittal T2-weighted turbo spin-echo (B) images show
homogeneously enhanced and intensely bright T2 signal of vaginal
pheochromocytoma (arrow).
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Syndromes Associated with Pheochromocytoma
Multiple Endocrine Neoplasia
In multiple endocrine neoplasias (MEN2), pheochromocytoma is associated
with medullary carcinoma of the thyroid (Figs.
8A and
8B). In type MEN2A,
hyperparathyroidism also occurs. In type MEN2B, mucous schwannomas, a
marfanoid habitus, and labial hypertrophy are often observed. The prevalence
of pheochromocytoma in MEN2 is 50% (type 2A) and 90% (type 2B), with
unilateral involvement being twice as common as bilateral involvement
[7].
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Fig. 8A. —45-year-old man who was evaluated for hypertension 3 years after
removal of primary medullary thyroid cancer. Axial T2-weighted
inversion-recovery image shows right adrenal pheochromocytoma, exhibiting
bright T2 signal (thin arrow). Tiny hepatic metastasis is also seen
(thick arrow).
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Fig. 8B. —45-year-old man who was evaluated for hypertension 3 years after
removal of primary medullary thyroid cancer. Photomicrograph of biopsy
specimen of liver lesion shows metastatic medullary thyroid carcinoma with
nests of tumor cells with small, round nuclei in fibrotic stroma (lower right)
with normal liver (upper left). Tumor cells were positive for calcitonin by
immunohistochemistry.
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Von Hippel-Lindau Disease
Von Hippel-Lindau disease (VHL) is a congenital syndrome with autosomal
dominant transmission, a prevalence of 1/36,000, and complete penetrance by 65
years [8]. Clinical
manifestations and age of onset are variable. The most frequent tumors are
retinal angiomas, hemangioblastomas of the central nervous system, renal
cysts, clear cell carcinomas, pancreatic cysts, neuroendocrine tumors (Figs.
9A and
9B), tumors of the
endolymphatic sac, and epididymal cystadenoma. The prevalence of
pheochromocytoma in VHL is 20%
[9]. Absence or presence of
pheochromocytoma defines type 1 and 2 VHL
[7]. Follow-up with
cross-sectional imaging plays a central role in managing the disease.
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Fig. 9A. —49-year-old woman with von Hippel-Lindau disease. Axial
gradient-recalled echo (A) and axial turbo spin-echo T2-weighted
(B) images show right adrenal pheochromocytoma (white arrow),
left renal cyst (thin black arrow), and islet cell tumor affecting
pancreatic tail (thick black arrow).
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Fig. 9B. —49-year-old woman with von Hippel-Lindau disease. Axial
gradient-recalled echo (A) and axial turbo spin-echo T2-weighted
(B) images show right adrenal pheochromocytoma (white arrow),
left renal cyst (thin black arrow), and islet cell tumor affecting
pancreatic tail (thick black arrow).
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Von Recklinghausen Neurofibromatosis
Von Recklinghausen neurofibromatosis (NF1) has a prevalence of 1/5,000. NF1
predisposes an individual to tumors originating in the neuroectoderm.
Phenotypic signs of the disease are highly variable even among members of the
same family. Pheochromocytoma occurs more commonly in patients with NF1 than
in the general population (Fig.
10) [7].
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Fig. 10. —27-year-old man with neurofibromatosis 1. Axial T2-weighted
fat-saturated image shows T2 hyperintense left adrenal mass representing
pheochromocytoma (black arrow). Multiple subcutaneous neurofibromas
(white arrows) are also seen.
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Nonsyndromic Familial Pheochromocytoma
Some families have a genetic predisposition to develop pheochromocytoma in
isolation without associated conditions
[7].
Carney's Triad
The triad of gastric leiomyosarcoma, pulmonary chondroma, and
pheochromocytoma (most often extraadrenal and functioning) was first described
by Carney in 1977 [1]. The
cause of the Carney's triad is unknown, and only 58 cases have been reported
since its identification in 1977
[2].
Clinical Consideration
Although the clinical presentation is variable, most patients with
pheochromocytoma experience hypertensive crises. A hypertensive
crisis—acute severe elevation of blood pressure
[10]—may be precipitated
by abdominal trauma, physical activity, general anesthesia, surgical
manipulation, or, in the case of bladder pheochromocytoma, micturition.
Diagnostic Approach and the Role of MRI
Elevated levels of urinary metanephrine or resting plasma catecholamines
can suggest the diagnosis of pheochromocytoma (97% sensitivity for the urinary
catecholamines and 99% for plasma catecholamines)
[11]. After biochemical
testing suggests pheochromocytoma, imaging is necessary to establish tumor
location.
MRI is increasingly used because of its multiplanar capability, high
sensitivity for contrast enhancement, and lack of ionizing radiation. The
relative usefulness of MRI and I-131-metaiodobenzylguanidine (MIBG)
scintigraphy is controversial; in a series of 282 patients with
pheochromocytoma, MRI provided higher sensitivity than CT or MIBG scintigraphy
[12]. However, more recent
studies have shown a growing role of MIBG scintigraphy and CT in the
evaluation of pheochromocytomas
[13].
Half of pheochromocytomas are now identified incidentally on
cross-sectional imaging—this is a crucial reason why radiologists now,
more than ever, should understand the appearance of pheochromocytomas
[14].
On MRI, pheochromocytomas have been described as enhancing masses having
characteristic high signal intensity on T2-weighted imaging, best appreciated
with the use of fat suppression. They are typically heterogeneous. Although
the classic T2 appearance has been previously described as a light bulb bright
signal on T2-weighted imaging, this is neither specific nor sensitive, and the
use of this sign leads to the misdiagnosis of pheochromocytoma in up to 35% of
cases [15].
Pheochromocytomas do not contain intracytoplasmic lipid and maintain their
signal on opposed-phase gradient-echo images (Figs.
11A,
11B, and
11C). Namimoto et al.
[16] have reported 100%
sensitivity for differentiating pheochromocytoma from adrenal adenomas, on the
basis of lack of dropout of signal intensity on opposed-phase images. Using
the current low-density CT criteria for diagnosing adrenal adenoma can be
misleading because it has been reported that pheochromocytomas can have low
attenuation values similar to those of adenomas
[17].
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Fig. 11A. —39-year-old woman undergoing renal donor evaluation, with incidental
diagnosis of pheochromocytoma. Gradient-recalled echo in-phase (A) and
opposed-phase (B) images with TR of 205 msec and TE values of 2.4 msec
for opposed-phase images and 4.2 msec for in-phase images show no signal
dropout on opposed-phase chemical-shift imaging.
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Fig. 11B. —39-year-old woman undergoing renal donor evaluation, with incidental
diagnosis of pheochromocytoma. Gradient-recalled echo in-phase (A) and
opposed-phase (B) images with TR of 205 msec and TE values of 2.4 msec
for opposed-phase images and 4.2 msec for in-phase images show no signal
dropout on opposed-phase chemical-shift imaging.
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Fig. 11C. —39-year-old woman undergoing renal donor evaluation, with incidental
diagnosis of pheochromocytoma. Axial T2-weighted fat-saturated image shows
bright T2 signal typical of pheochromocytoma.
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Many lesions show intense contrast enhancement
[3]. A characteristic
salt-and-pepper pattern has also been described; serpiginous areas of signal
void representing high vascular flow may be interspersed among areas of high
signal intensity caused by slowly flowing blood and tumor cells
[18] (Figs.
1A,
1B, and
6D).
MRI Protocol
Our protocol for imaging of the abdomen in patients with suspected
pheochromocytoma includes the following sequences: coronal breath-hold T2
HASTE; gradient-recalled echo T1 chemical-shift imaging with in- and
opposed-phase breath-hold images obtained in the axial plane; fast spin-echo
T2-weighted fat-saturated or long TE inversion-recovery breath-hold images
obtained in the axial plane; and pre-contrast and dynamic-enhanced
gradient-recalled-echo 3D volumetric interpolated breath-hold examination
images obtained in the axial plane. Anatomic coverage should extend from the
diaphragm to the aortic bifurcation.
Conclusion
MRI is emerging as the technique of choice for the diagnosis of
pheochromocytomas, given its ability to safely detect the lesions and
differentiate them from adrenal adenomas. In cases of suspected extraadrenal
pheochromocytoma, a combination of biochemical tests, MIBG scintigraphy, and
MRI may be useful for detection and characterization of such lesions.
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Introduction
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