CASE REPORT

Posterior mediastinal paraganglioma with bilateraladrenal pheochromocytoma

H.J. Kwona, J.H. Parka, G.Y. Jinb, M.J. Chungc, S.T. Limd, M.H. Kime,H.J. Kimf, Y.C. Leea,*

aDepartment of Internal Medicine, Chonbuk National University Hospital, 634-18, Jeonju 561-712, SouthKoreabDepartment of Diagnostic Radiology, Chonbuk National University Hospital, Jeonju, South KoreacDepartment of Pathology, Chonbuk National University Hospital, Jeonju, South KoreadDaepartment of Nuclear Medicine, Chonbuk National University Hospital, Jeonju, South KoreaeDepartment of Thoracic Surgery, Chonbuk National University Hospital, Jeonju, South KoreafDepartment of Urology, Chonbuk National University Hospital, Jeonju, South Korea

Summary Paraganglioma and adrenal pheochromocytoma are tumors of commonorigin arising from chromaffin cells. However, it is extremely rare to find mediastinalparaganglioma simultaneously with bilateral adrenal pheochromocytoma. We reporta 53-year-old man who was diagnosed with posterior mediastinal paraganglioma andbilateral adrenal pheochromocytoma and who underwent successful excision of theposterior mediastinal mass and bilateral total adrenalectomy.& 2004 Elsevier Ltd. All rights reserved.

A 53-year-old man was hospitalized for the evalua-tion of a posterior mediastinal mass in March 2002.The patient’s medical history was as follows: about20 years ago, he was treated with an oralantituberculosis medication due to pulmonarytuberculosis. About 10 years ago, he was diagnosedwith hypertension and bilateral adrenal pheochro-mocytoma at another hospital and was treated withalpha-blockers without surgical resection. He hasbeen hospitalized repeatedly because of recurrenthemoptysis due to earlier pulmonary tuberculosissince 1995, and he underwent bronchial arterialembolization because of massive hemoptysis. Atthat time, a chest computed tomography (CT)

showed a 4 cm well-enhanced mass in his posteriormediastinum, but he declined further evaluation ofthe mass. The size of mass had not changed at afollow-up chest CT scan undertaken in February2002 (Fig. 1A). The patient’s family history wasnegative.

For the evaluation of the posterior mediastinalmass, a percutaneous needle biopsy was performedand pathologic findings showed paraganglioma.Hormonal assays and magnetic resonance (MR)images of the patient’s abdomen were performedto evaluate bilateral adrenal pheochromocytoma.Levels of 24-h urinary metanephrine, vanillylman-delic acid and serum norepinephrine (4.9mg/day,26.8mg/day and 2408 pg/ml, respectively) wereelevated. However, the serum parathormone leveland the serum calcitonin level were in the normalrange (23.96 and 0.3 pg/ml, respectively). The MR

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KEYWORDS

Posterior mediastinal para-

ganglioma;

Bilateral adrenal pheo-

chromocytoma;

Iodine-131 metaiodoben-

zylguanidine scintigraphy

*Corresponding author. Tel.: þ 82-63-250-1664; fax: þ 82-63-254-1609.E-mail address: leeyc@moak.chonbuk.ac.kr (Y.C. Lee).

0954-6111/$ - see front matter & 2004 Elsevier Ltd. All rights reserved.doi:10.1016/j.rmed.2003.12.001

Respiratory Medicine (2004) 98, 574–576

image of the bilateral adrenal masses was compa-tible with pheochromocytoma (not shown). In 72 h-delayed whole-body images using Iodine-131 me-taiodobenzylguanidine (131I-MIBG) scintigraphy, bi-lateral but asymmetric increased radioactivities inboth adrenal glands were observed (Fig. 1B);radioactivities in the left adrenal gland are muchlarger than in the right adrenal gland, whichappears as a small coin-like shape. However, noradioactivity is seen in the posterior mediastinalmass lesion and other sites considered as abnormalfindings.

In April 2002, the patient underwent surgery.After the excision of the 4.5� 3.0� 2.5 cm3 tumorin the posterior mediastinum, a bilateral totaladrenalectomy was performed. The size of the leftadrenal mass (5.2� 4.5� 3.7 cm3) was much largerthan the right adrenal mass (1.0� 0.9� 0.8 cm3).Microscopically, surgical specimens of the adrenaland posterior mediastinal masses showed typicalfindings of pheochromocytoma and paraganglioma,respectively (Fig. 1C and D); the two lesions show asimilar growth pattern; polygonal cells with sharplydefined border are arranged in irregular nests

around a delicate vasculature (Zellballen pattern).Immunohistochemical staining is markedly positivefor neuron-specific enolase and chromogranin.There is no finding of malignancy; mitosis is veryrare (less than 1 per 30 high power field). Moreover,hemorrhage, necrosis and invasion to surroundingtissue and vessels are not seen. The posteriormediastinal mass was surrounded by normal para-ganglion tissues (Fig. 1E); paraganglion tissueincluding ganglion cells and peripheral nervebundles around the mass are seen.

Discussion

Paragangliomas (extra-adrenal pheochromocyto-mas) are rare tumors arising from extra-adrenalchromaffin tissues that are derived from the neuralcrest. The most common site of paragangliomas isthe region between the diaphragm and the inferiorrenal poles and at least 85% of all extra-adrenalpheochromocytomas have been found below thediaphragm.1 Our case is quite rare in that the

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Figure 1 (A) A contrast-enhanced CT scan showing an enhancement of the tumor in the left paraspinal area. (B) 131I-MIBG scintigraphy 72 h after the intravenous injection of 111MBq (3mCi). (C) Adrenal mass in right adrenal gland(chromogranin, 200� ). (D) Posterior mediastinal mass (chromogranin, 200� ). (E) Normal paraganglion tissue aroundthe posterior mediastinal mass (hematoxylin–eosin, 40� ).

Posterior mediastinal paraganglioma with bilateral adrenal pheochromocytoma 575

patient had a posterior mediastinal paragangliomaand bilateral adrenal pheochromocytoma concur-rently. Rare cases of multifocal tumors have beenreported in diseases with genetic abnormality. One-third of multiple endocrine neoplasia (MEN) type 2or Von Hippel–Lindau disease have been presentedas bilateral pheochromocytoma.2 The bilateralitysuggests a multicentric origin in the developmentof these tumors. But, it is extremely rare multifocaltumors in sporadic case like this patient.

It is important to investigate the entire body inpatients suspecting pheochromocytomas becausepheochromocytomas may arise in extra-adrenallocations in about 18% of patients.1 In our patient,we were not able to detect the posterior mediast-inal mass earlier because we did not examine theentire body carefully. For this purpose, 131I-MIBGscintigraphy is very useful to detect extra-adrenaldisease, especially in the examination of post-operative recurrence or malignant metastatic dis-ease.3,4 The high efficacy of 131I-MIBG scintigraphyfor the detection of phechromocytoma is wellknown. However, there was no uptake of 131I-MIBGin the posterior mediastinal lesion in this case. Afalse-negative rate of about 10% has been re-ported.5,6 Although the exact reasons are unknown,the most likely explanation is variability in thespectrum of uptake capacity. 131I-MIBG enterspheochromocytoma cells by two different path-ways. Type I amine uptake is a specific, energy-requiring, sodium-dependent and saturablemechanism, which predominates when the concen-tration of MIBG is less than 10 mM/l. Type II uptake(nonspecific, energy-independent, diffusional me-chanism) occurs at higher concentrations.7,8 Theuptake of 131I-MIBG is believed to be mainly due tothe type I mechanism and subsequent storage incatecholamine-storage granules. On the otherhand, it is also possible that a metastatic lesioncan have a different scintigraphic quality than theprimary tumor. But, we could not find any casereports about the difference in scintigraphicquality between metastatic lesion and primaryfocus of pheochromocytoma. If a lesion is the truemetastatic lesion from the primary tumor, thenature of uptake of radioisotope will be the samebecause they have the identical histologic features.

At first, we had thought that the posteriormediastinal mass might be a metastatic lesion fromthe adrenal pheochromocytoma. However, we wereable to conclude that the thoracic mass was not a

metastatic lesion for the following reasons. First,the surgical specimen of the posterior mediastinalmass showed typical findings of paraganglioma andhad no malignant features. Second, the posteriormediastinal mass was surrounded by normal para-ganglion tissues. Malignant pheochromocytomahave the feature of extensive local invasion ormetastasis to sites where chromaffin tissue is notnormally present.9 Third, the 131I-MIBG scintigraphyof the posterior mediastinal mass was negative,unlike the adrenal lesion.

In conclusion, paragangliomas can coexist withadrenal pheochromocytomas although the inci-dence is very rare. Therefore, clinicians who seepatients with adrenal pheochromocytomas shouldinvestigate the entire body. At this time, 131I-MIBGscintigraphy is very useful for initial examination,but careful attention is required because of thepossibility of a false negative.

References

1. Whalen RK, Aithausen AF, Daniels GH. Extra-adrenalpheochromocytoma: review article. J Urol 1992;147:1–10.

2. Hoffman RW, Gardner DW, Mitchell FL. Intrathoracic andmultiple abdominal pheochromocytomas in von Hippel–Lindau disease. Arch Intern Med 1982;142:1962–4.

3. Maurea S, Cuocolo A, Reynolds JC, et al. Iodine-131-metaiodobenzylguanidine scintigraphy in preoperative andpostoperative evaluation of paragangliomas: comparison withCT and MRI. J Nucl Med 1993;34:173–6.

4. Quint LE, Glazer GM, Francis IR, Shapiro B, Chenevert TL.Pheochromocytoma and paraganglioma: comparison of MRimaging with CT and I-131 MIBG scintigraphy. Radiology1987;165:89–93.

5. Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, BeierwaltesWH. Iodine-131 metaiodobenzylguanidine for the location ofsuspected pheochromocytoma: experience in 400 cases.J Nucl Med 1985;26:576–85.

6. Chatal JF, Charbonnel B. Comparison of iodobenzylguanidineimaging with computed tomography in locating pheochromo-cytoma. J Clin Endocrinol Metab 1985;61:769–72.

7. Jacques S, Tobes MC, Sisson JC, Baker JA, Wieland DM.Comparison of the sodium dependency of uptake of meta-iodobenzylguanidine and norepinephrine into cultured bovineadrenomedullary cells. Mol Pharmacol 1984;26:539–46.

8. Jacques S, Tobes MC, Sisson JC. Sodium dependency of uptakeof norepinephrine and m-iodobenzylguanidine into culturedhuman pheochromocytoma cells: evidence for uptake-one.Cancer Res 1987;47:3920–8.

9. Neville AM. The adrenal medulla. In: Symington T, editor.Functional pathology of the human adrenal gland. Baltimore:Williams and Wilkins; 1969. p. 217–324.

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