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AJR 2005;184:860–867 0361–803X/05/1843–860 © American Roentgen Ray Society

MR ImagingElsayes et al.MRI of Pheochromocytoma

Pictorial Essay

MRI of Adrenal and Extraadrenal PheochromocytomaKhaled M. Elsayes1, Vamsidhar R. Narra1, John R. Leyendecker2, Isaac R. Francis3, James S. Lewis, Jr.4, Jeffrey J. Brown

Elsayes KM, Narra VR, Leyendecker JR, Francis IR, Lewis JS Jr, Brown JJ1

heochromocytomas are uncommontumors arising from pheochro-mocytes, the predominant cells ofadrenal medulla. These tumors also

arise in the paraganglia near the aorta and theganglia of the sympathetic chains. The pheo-

chromocytes constitute the chromaffin system.Chromaffin cells are widespread and are associ-ated with sympathetic ganglia during fetal life.Most chromaffin cells degenerate after birth,with the majority of residual cells remaining inthe adrenal medulla [1]. This may explain why

approximately 90% of pheochromocytomas oc-cur in the adrenal medulla [1].

EpidemiologyPheochromocytomas are most common in

the fourth through sixth decades of life.

Received May 13, 2004; accepted after revision August 26, 2004.

1Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd., St. Louis, MO 63110. Address correspondence to V. R. Narra (narrav@mir.wustl.edu).2Department of Radiology, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157.3Department of Radiology, University of Michigan, Ann Arbor, MI.4Department of Surgical Pathology, Washington University School of Medicine, St. Louis, MO 63110.

P

A B

Fig. 1.—41-year-old woman with hypertension.A and B, Coronal HASTE (A) and axial contrast-enhanced volumetric interpolated breath-hold examination (B) images show bilateral adrenal masses exhibiting bright T2 sig-nal intensity with salt-and-pepper enhancement pattern representing bilateral pheochromocytomas (arrows).

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Women and men are affected with similarfrequency. Pheochromocytoma has beencalled the 10% tumor because approxi-mately 10% are bilateral (Fig. 1), 10% aremalignant, 10% occur in children, and 10%are extraadrenal. The extraadrenal lesionsare also referred to as paragangliomas [2]. Itis difficult to differentiate benign and malig-nant pheochromocytomas, histologically.Therefore, malignancy is usually establishedby local invasion or metastases to nonchro-maffin tissues. The most common sites ofmetastasis include bone, regional lymphnodes, liver, lung, and brain (Fig. 2). Extraa-drenal pheochromocytomas have a higherprevalence of malignancy than their adrenalcounterparts [3].

PathologyPheochromocytomas are well-circum-

scribed homogeneous masses that vary frompink to brown to red, depending on theirvascularity. Microscopically, they consist ofwell-defined nests (Zellballen) of rounded topolygonal cells with moderately abundantgranular cytoplasm and rounded to slightlyspindled nuclei with a speckled chromatinpattern. Mitoses are rare. The cell nests areseparated by vascular septa and, at their pe-

riphery, have stellate (sustentacular) support-ing cells [4].

LocationsPheochromocytomas arise from the adre-

nal medulla and the sympathetic paragan-glia. Sympathetic ganglia are foundpredominantly in the paraaxial region of thetrunk along the prevertebral and paraverte-bral sympathetic chains and in the connec-tive tissue in or near the walls of pelvicorgans. Most pheochromocytomas are lo-cated in the abdomen (98%), with most aris-ing from the adrenal gland. Extraadrenalpheochromocytomas are associated with theceliac, superior mesenteric, and inferior me-senteric ganglia, which are retroperitoneal inlocation. The organ of Zuckerkandl is theonly macroscopic extraadrenal sympatheticparaganglion, located at the origin of inferiormesenteric artery [5] (Fig. 3). Approxi-mately 1% of pheochromocytomas occur inthe thorax, including paravertebral posteriormediastinal pheochromocytomas (Fig. 4).Intrapericardial pheochromocytomas havebeen described as typically located adjacentto or involving the left atrium (Fig. 5). Sym-pathetic ganglia are particularly numerousalong the fibers of the inferior hypogastric

plexus, leading to and entering the urogeni-tal organs (Fig. 6). Pheochromocytomas ofthe female genital tract are exceptionallyrare with only 10 cases reported in detailsince 1926, with three of these arising in thevagina [6] (Fig. 7).

Syndromes Associated with PheochromocytomaMultiple Endocrine Neoplasia

In multiple endocrine neoplasias (MEN2),pheochromocytoma is associated with medullarycarcinoma of the thyroid (Fig. 8). In typeMEN2A, hyperparathyroidism also occurs. Intype MEN2B, mucous schwannomas, amarfanoid habitus, and labial hypertrophy are of-ten observed. The prevalence of pheochromocy-toma in MEN2 is 50% (type 2A) and 90% (type2B), with unilateral involvement being twice ascommon as bilateral involvement [7].

Von Hippel-Lindau DiseaseVon Hippel-Lindau disease (VHL) is a

congenital syndrome with autosomal domi-nant transmission, a prevalence of 1/36,000,and complete penetrance by 65 years [8].Clinical manifestations and age of onset arevariable. The most frequent tumors are reti-nal angiomas, hemangioblastomas of the

A B

Fig. 2.—52-year-old man with incidentally seen, pathologically proven metastatic deposits.A and B, Axial contrast-enhanced T1-weighted 3D volumetric interpolated breath-hold examination image (A) and axial inversion-recovery image (B) show enhancing liverlesion and bright T2 signal within vertebral body representing metastases from malignant pheochromocytoma 7 years after surgical removal of tumor.

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A B

Fig. 3.—37-year-old woman with retroperitoneal mass seen on CT scan.A and B, Axial enhanced gradient-refocused echo T1-weighted fat-saturated (A) and coronal T2-weighted HASTE (B) images show left paraaortic well-defined pheochro-mocytoma, exhibiting intensely bright T2 signal (arrow).

Fig. 4.—32-year-old man with hypertension.Axial T1-weighted gradient-refocused echo sequence after gadolinium-chelateinjection shows markedly enhancing mediastinal pheochromocytoma (arrow).

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central nervous system, renal cysts, clearcell carcinomas, pancreatic cysts, neuroendo-crine tumors (Fig. 9), tumors of the endolym-phatic sac, and epididymal cystadenoma.The prevalence of pheochromocytoma inVHL is 20% [9]. Absence or presence ofpheochromocytoma defines type 1 and 2VHL [7]. Follow-up with cross-sectionalimaging plays a central role in managingthe disease.

Von Recklinghausen NeurofibromatosisVon Recklinghausen neurofibromatosis

(NF1) has a prevalence of 1/5,000. NF1predisposes an individual to tumors origi-nating in the neuroectoderm. Phenotypicsigns of the disease are highly variable evenamong members of the same family. Pheo-chromocytoma occurs more commonly inpatients with NF1 than in the general popu-lation (Fig. 10) [7].

Nonsyndromic Familial PheochromocytomaSome families have a genetic predisposi-

tion to develop pheochromocytoma in iso-lation without associated conditions [7].

Carney’s TriadThe triad of gastric leiomyosarcoma, pul-

monary chondroma, and pheochromocytoma(most often extraadrenal and functioning)was first described by Carney in 1977 [1]. Thecause of the Carney’s triad is unknown, andonly 58 cases have been reported since itsidentification in 1977 [2].

Clinical ConsiderationAlthough the clinical presentation is

variable, most patients with pheochromocy-toma experience hypertensive crises. A hy-pertensive crisis—acute severe elevation ofblood pressure [10]—may be precipitatedby abdominal trauma, physical activity,general anesthesia, surgical manipulation,or, in the case of bladder pheochromocy-toma, micturition.

Diagnostic Approach and the Role of MRIElevated levels of urinary metanephrine or

resting plasma catecholamines can suggest thediagnosis of pheochromocytoma (97% sensitiv-ity for the urinary catecholamines and 99% forplasma catecholamines) [11]. After biochemi-

cal testing suggests pheochromocytoma, imag-ing is necessary to establish tumor location.

MRI is increasingly used because of itsmultiplanar capability, high sensitivity forcontrast enhancement, and lack of ionizingradiation. The relative usefulness of MRI andI- 131-metaiodobenzylguanidine (MIBG) scin-tigraphy is controversial; in a series of 282 pa-tients with pheochromocytoma, MRI providedhigher sensitivity than CT or MIBG scintigra-phy [12]. However, more recent studies haveshown a growing role of MIBG scintigraphyand CT in the evaluation of pheochromocyto-mas [13].

Half of pheochromocytomas are nowidentified incidentally on cross-sectional im-aging—this is a crucial reason why radiolo-gists now, more than ever, should understandthe appearance of pheochromocytomas [14].

On MRI, pheochromocytomas have beendescribed as enhancing masses having char-acteristic high signal intensity on T2-weighted imaging, best appreciated with theuse of fat suppression. They are typicallyheterogeneous. Although the classic T2 ap-pearance has been previously described as a

A B

Fig. 5.—18-year-old man with hypertension and mediastinal mass seen on echocardiography.A and B, Contrast-enhanced sagittal T1- (A) and axial T2 -weighted (B) images of heart show intensely enhancing, bright T2 signal mass representing intrapericardial pheo-chromocytoma (arrow) adjacent to left atrium.

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C D

Fig. 6.—42-year-old man with multiple endocrine neoplasia (MEN2).A–D, 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 pre-sacral lesion (arrow), bright on T2 with intense contrast enhancement, in this case of intrapelvic presacral pheochromocytoma. Axial contrast-enhanced volumetric interpolatedbreath-hold examination image (D) shows left adrenal mass (exhibiting salt-and-pepper contrast-enhancement pattern), representing adrenal pheochromocytoma (arrow).

A B

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A BFig. 8.—45-year-old man who was evaluated for hypertension 3 years after removal of primary medullary thyroid cancer.A, Axial T2-weighted inversion-recovery image shows right adrenal pheochromocytoma, exhibiting bright T2 signal (thin arrow). Tiny hepatic metastasis is also seen (thick arrow).B, 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.

A BFig. 7.—37-year-old woman with postcoital headache and fainting spells.A and B, Axial contrast-enhanced gradient-refocused echo T1-weighted fat-saturated (A) and sagittal T2-weighted turbo spin-echo (B) images show homogeneouslyenhanced and intensely bright T2 signal of vaginal pheochromocytoma (arrow).

A BFig. 9.—49-year-old woman with von Hippel-Lindau disease.A and B, Axial gradient-recalled echo (A) and axial turbo spin-echo T2-weighted (B) images show right adrenal pheochromocytoma (white arrow), left renal cyst (thin blackarrow), and islet cell tumor affecting pancreatic tail (thick black arrow).

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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 rep-resenting pheochromocytoma (black arrow). Multiple subcutaneous neurofibromas(white arrows) are also seen.

A B

Fig. 11.—39-year-old woman undergoing renal donor evaluation, with incidentaldiagnosis of pheochromocytoma.A and B, Gradient-recalled echo in-phase (A) and opposed-phase (B) images with TR of205 msec and TE values of 2.4 msec for opposed-phase images and 4.2 msec for in-phaseimages show no signal dropout on opposed-phase chemical-shift imaging.C, Axial T2-weighted fat-saturated image shows bright T2 signal typical of pheochro-mocytoma.

C

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light bulb bright signal on T2-weighted im-aging, this is neither specific nor sensitive,and the use of this sign leads to the misdiag-nosis of pheochromocytoma in up to 35% ofcases [15].

Pheochromocytomas do not containintracytoplasmic lipid and maintain theirsignal on opposed-phase gradient-echoimages (Fig. 11). Namimoto et al. [16]have reported 100% sensitivity for differ-entiating pheochromocytoma from adre-nal adenomas, on the basis of lack ofdropout of signal intensity on opposed-phase images. Using the current low-den-sity CT criteria for diagnosing adrenal ad-enoma can be misleading because it hasbeen reported that pheochromocytomascan have low attenuation values similar tothose of adenomas [17].

Many lesions show intense contrast enhance-ment [3]. A characteristic salt-and-pepper pat-tern has also been described; serpiginous areasof signal void representing high vascular flowmay be interspersed among areas of high signalintensity caused by slowly flowing blood and tu-mor cells [18] (Figs. 1 and 6D).

MRI ProtocolOur protocol for imaging of the abdomen

in patients with suspected pheochromocy-toma includes the following sequences: coro-nal breath-hold T2 HASTE; gradient-recalledecho T1 chemical-shift imaging with in- andopposed-phase breath-hold images obtainedin the axial plane; fast spin-echo T2-weightedfat-saturated or long TE inversion-recoverybreath-hold images obtained in the axialplane; and pre-contrast and dynamic-en-

hanced gradient-recalled-echo 3D volumetricinterpolated breath-hold examination imagesobtained in the axial plane. Anatomic cover-age should extend from the diaphragm to theaortic bifurcation.

ConclusionMRI is emerging as the technique of choice

for the diagnosis of pheochromocytomas,given its ability to safely detect the lesionsand differentiate them from adrenal ade-nomas. In cases of suspected extraadrenalpheochromocytoma, a combination of bio-chemical tests, MIBG scintigraphy, and MRImay be useful for detection and characteriza-tion of such lesions.

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