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Posterior mediastinal paraganglioma with bilateral adrenal pheochromocytoma
ARTICLE IN PRESS Respiratory Medicine (2004) 98, 574–576
CASE REPORT
Posterior mediastinal paraganglioma with bilateral adrenal 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,* a
Department of Internal Medicine, Chonbuk National University Hospital, 634-18, Jeonju 561-712, South Korea b Department of Diagnostic Radiology, Chonbuk National University Hospital, Jeonju, South Korea c Department of Pathology, Chonbuk National University Hospital, Jeonju, South Korea d Daepartment of Nuclear Medicine, Chonbuk National University Hospital, Jeonju, South Korea e Department of Thoracic Surgery, Chonbuk National University Hospital, Jeonju, South Korea f Department of Urology, Chonbuk National University Hospital, Jeonju, South Korea
KEYWORDS Posterior mediastinal paraganglioma; Bilateral adrenal pheochromocytoma; Iodine-131 metaiodobenzylguanidine scintigraphy
Summary Paraganglioma and adrenal pheochromocytoma are tumors of common origin arising from chromaffin cells. However, it is extremely rare to find mediastinal paraganglioma simultaneously with bilateral adrenal pheochromocytoma. We report a 53-year-old man who was diagnosed with posterior mediastinal paraganglioma and bilateral adrenal pheochromocytoma and who underwent successful excision of the posterior mediastinal mass and bilateral total adrenalectomy. & 2004 Elsevier Ltd. All rights reserved.
A 53-year-old man was hospitalized for the evaluation of a posterior mediastinal mass in March 2002. The patient’s medical history was as follows: about 20 years ago, he was treated with an oral antituberculosis medication due to pulmonary tuberculosis. About 10 years ago, he was diagnosed with hypertension and bilateral adrenal pheochromocytoma at another hospital and was treated with alpha-blockers without surgical resection. He has been hospitalized repeatedly because of recurrent hemoptysis due to earlier pulmonary tuberculosis since 1995, and he underwent bronchial arterial embolization because of massive hemoptysis. At that time, a chest computed tomography (CT) *Corresponding author. Tel.: þ 82-63-250-1664; fax: þ 82-63254-1609. E-mail address: [email protected] (Y.C. Lee).
showed a 4 cm well-enhanced mass in his posterior mediastinum, but he declined further evaluation of the mass. The size of mass had not changed at a follow-up chest CT scan undertaken in February 2002 (Fig. 1A). The patient’s family history was negative. For the evaluation of the posterior mediastinal mass, a percutaneous needle biopsy was performed and pathologic findings showed paraganglioma. Hormonal assays and magnetic resonance (MR) images of the patient’s abdomen were performed to evaluate bilateral adrenal pheochromocytoma. Levels of 24-h urinary metanephrine, vanillylmandelic acid and serum norepinephrine (4.9 mg/day, 26.8 mg/day and 2408 pg/ml, respectively) were elevated. However, the serum parathormone level and the serum calcitonin level were in the normal range (23.96 and 0.3 pg/ml, respectively). The MR
0954-6111/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2003.12.001
ARTICLE IN PRESS Posterior mediastinal paraganglioma with bilateral adrenal pheochromocytoma
575
Figure 1 (A) A contrast-enhanced CT scan showing an enhancement of the tumor in the left paraspinal area. (B) 131IMIBG scintigraphy 72 h after the intravenous injection of 111 MBq (3 mCi). (C) Adrenal mass in right adrenal gland (chromogranin, 200 ). (D) Posterior mediastinal mass (chromogranin, 200 ). (E) Normal paraganglion tissue around the posterior mediastinal mass (hematoxylin–eosin, 40 ).
image of the bilateral adrenal masses was compatible with pheochromocytoma (not shown). In 72 hdelayed whole-body images using Iodine-131 metaiodobenzylguanidine (131I-MIBG) scintigraphy, bilateral but asymmetric increased radioactivities in both adrenal glands were observed (Fig. 1B); radioactivities in the left adrenal gland are much larger than in the right adrenal gland, which appears as a small coin-like shape. However, no radioactivity is seen in the posterior mediastinal mass lesion and other sites considered as abnormal findings. In April 2002, the patient underwent surgery. After the excision of the 4.5 3.0 2.5 cm3 tumor in the posterior mediastinum, a bilateral total adrenalectomy was performed. The size of the left adrenal mass (5.2 4.5 3.7 cm3) was much larger than the right adrenal mass (1.0 0.9 0.8 cm3). Microscopically, surgical specimens of the adrenal and posterior mediastinal masses showed typical findings of pheochromocytoma and paraganglioma, respectively (Fig. 1C and D); the two lesions show a similar growth pattern; polygonal cells with sharply defined border are arranged in irregular nests
around a delicate vasculature (Zellballen pattern). Immunohistochemical staining is markedly positive for neuron-specific enolase and chromogranin. There is no finding of malignancy; mitosis is very rare (less than 1 per 30 high power field). Moreover, hemorrhage, necrosis and invasion to surrounding tissue and vessels are not seen. The posterior mediastinal mass was surrounded by normal paraganglion tissues (Fig. 1E); paraganglion tissue including ganglion cells and peripheral nerve bundles around the mass are seen.
Discussion Paragangliomas (extra-adrenal pheochromocytomas) are rare tumors arising from extra-adrenal chromaffin tissues that are derived from the neural crest. The most common site of paragangliomas is the region between the diaphragm and the inferior renal poles and at least 85% of all extra-adrenal pheochromocytomas have been found below the diaphragm.1 Our case is quite rare in that the
ARTICLE IN PRESS 576
patient had a posterior mediastinal paraganglioma and bilateral adrenal pheochromocytoma concurrently. Rare cases of multifocal tumors have been reported in diseases with genetic abnormality. Onethird of multiple endocrine neoplasia (MEN) type 2 or Von Hippel–Lindau disease have been presented as bilateral pheochromocytoma.2 The bilaterality suggests a multicentric origin in the development of these tumors. But, it is extremely rare multifocal tumors in sporadic case like this patient. It is important to investigate the entire body in patients suspecting pheochromocytomas because pheochromocytomas may arise in extra-adrenal locations in about 18% of patients.1 In our patient, we were not able to detect the posterior mediastinal mass earlier because we did not examine the entire body carefully. For this purpose, 131I-MIBG scintigraphy is very useful to detect extra-adrenal disease, especially in the examination of postoperative recurrence or malignant metastatic disease.3,4 The high efficacy of 131I-MIBG scintigraphy for the detection of phechromocytoma is well known. However, there was no uptake of 131I-MIBG in the posterior mediastinal lesion in this case. A false-negative rate of about 10% has been reported.5,6 Although the exact reasons are unknown, the most likely explanation is variability in the spectrum of uptake capacity. 131I-MIBG enters pheochromocytoma cells by two different pathways. Type I amine uptake is a specific, energyrequiring, sodium-dependent and saturable mechanism, which predominates when the concentration of MIBG is less than 10 mM/l. Type II uptake (nonspecific, energy-independent, diffusional mechanism) occurs at higher concentrations.7,8 The uptake of 131I-MIBG is believed to be mainly due to the type I mechanism and subsequent storage in catecholamine-storage granules. On the other hand, it is also possible that a metastatic lesion can have a different scintigraphic quality than the primary tumor. But, we could not find any case reports about the difference in scintigraphic quality between metastatic lesion and primary focus of pheochromocytoma. If a lesion is the true metastatic lesion from the primary tumor, the nature of uptake of radioisotope will be the same because they have the identical histologic features. At first, we had thought that the posterior mediastinal mass might be a metastatic lesion from the adrenal pheochromocytoma. However, we were able to conclude that the thoracic mass was not a
H.J. Kwon et al.
metastatic lesion for the following reasons. First, the surgical specimen of the posterior mediastinal mass showed typical findings of paraganglioma and had no malignant features. Second, the posterior mediastinal mass was surrounded by normal paraganglion tissues. Malignant pheochromocytoma have the feature of extensive local invasion or metastasis to sites where chromaffin tissue is not normally present.9 Third, the 131I-MIBG scintigraphy of the posterior mediastinal mass was negative, unlike the adrenal lesion. In conclusion, paragangliomas can coexist with adrenal pheochromocytomas although the incidence is very rare. Therefore, clinicians who see patients with adrenal pheochromocytomas should investigate the entire body. At this time, 131I-MIBG scintigraphy is very useful for initial examination, but careful attention is required because of the possibility of a false negative.
References 1. Whalen RK, Aithausen AF, Daniels GH. Extra-adrenal pheochromocytoma: review article. J Urol 1992;147: 1–10. 2. Hoffman RW, Gardner DW, Mitchell FL. Intrathoracic and multiple abdominal pheochromocytomas in von Hippel– Lindau disease. Arch Intern Med 1982;142:1962–4. 3. Maurea S, Cuocolo A, Reynolds JC, et al. Iodine-131metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: comparison with CT 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 MR imaging with CT and I-131 MIBG scintigraphy. Radiology 1987;165:89–93. 5. Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, Beierwaltes WH. Iodine-131 metaiodobenzylguanidine for the location of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 1985;26:576–85. 6. Chatal JF, Charbonnel B. Comparison of iodobenzylguanidine imaging with computed tomography in locating pheochromocytoma. 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 metaiodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol 1984;26:539–46. 8. Jacques S, Tobes MC, Sisson JC. Sodium dependency of uptake of norepinephrine and m-iodobenzylguanidine into cultured human 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.
CASE REPORT
Posterior mediastinal paraganglioma with bilateral adrenal 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,* a
Department of Internal Medicine, Chonbuk National University Hospital, 634-18, Jeonju 561-712, South Korea b Department of Diagnostic Radiology, Chonbuk National University Hospital, Jeonju, South Korea c Department of Pathology, Chonbuk National University Hospital, Jeonju, South Korea d Daepartment of Nuclear Medicine, Chonbuk National University Hospital, Jeonju, South Korea e Department of Thoracic Surgery, Chonbuk National University Hospital, Jeonju, South Korea f Department of Urology, Chonbuk National University Hospital, Jeonju, South Korea
KEYWORDS Posterior mediastinal paraganglioma; Bilateral adrenal pheochromocytoma; Iodine-131 metaiodobenzylguanidine scintigraphy
Summary Paraganglioma and adrenal pheochromocytoma are tumors of common origin arising from chromaffin cells. However, it is extremely rare to find mediastinal paraganglioma simultaneously with bilateral adrenal pheochromocytoma. We report a 53-year-old man who was diagnosed with posterior mediastinal paraganglioma and bilateral adrenal pheochromocytoma and who underwent successful excision of the posterior mediastinal mass and bilateral total adrenalectomy. & 2004 Elsevier Ltd. All rights reserved.
A 53-year-old man was hospitalized for the evaluation of a posterior mediastinal mass in March 2002. The patient’s medical history was as follows: about 20 years ago, he was treated with an oral antituberculosis medication due to pulmonary tuberculosis. About 10 years ago, he was diagnosed with hypertension and bilateral adrenal pheochromocytoma at another hospital and was treated with alpha-blockers without surgical resection. He has been hospitalized repeatedly because of recurrent hemoptysis due to earlier pulmonary tuberculosis since 1995, and he underwent bronchial arterial embolization because of massive hemoptysis. At that time, a chest computed tomography (CT) *Corresponding author. Tel.: þ 82-63-250-1664; fax: þ 82-63254-1609. E-mail address: [email protected] (Y.C. Lee).
showed a 4 cm well-enhanced mass in his posterior mediastinum, but he declined further evaluation of the mass. The size of mass had not changed at a follow-up chest CT scan undertaken in February 2002 (Fig. 1A). The patient’s family history was negative. For the evaluation of the posterior mediastinal mass, a percutaneous needle biopsy was performed and pathologic findings showed paraganglioma. Hormonal assays and magnetic resonance (MR) images of the patient’s abdomen were performed to evaluate bilateral adrenal pheochromocytoma. Levels of 24-h urinary metanephrine, vanillylmandelic acid and serum norepinephrine (4.9 mg/day, 26.8 mg/day and 2408 pg/ml, respectively) were elevated. However, the serum parathormone level and the serum calcitonin level were in the normal range (23.96 and 0.3 pg/ml, respectively). The MR
0954-6111/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2003.12.001
ARTICLE IN PRESS Posterior mediastinal paraganglioma with bilateral adrenal pheochromocytoma
575
Figure 1 (A) A contrast-enhanced CT scan showing an enhancement of the tumor in the left paraspinal area. (B) 131IMIBG scintigraphy 72 h after the intravenous injection of 111 MBq (3 mCi). (C) Adrenal mass in right adrenal gland (chromogranin, 200 ). (D) Posterior mediastinal mass (chromogranin, 200 ). (E) Normal paraganglion tissue around the posterior mediastinal mass (hematoxylin–eosin, 40 ).
image of the bilateral adrenal masses was compatible with pheochromocytoma (not shown). In 72 hdelayed whole-body images using Iodine-131 metaiodobenzylguanidine (131I-MIBG) scintigraphy, bilateral but asymmetric increased radioactivities in both adrenal glands were observed (Fig. 1B); radioactivities in the left adrenal gland are much larger than in the right adrenal gland, which appears as a small coin-like shape. However, no radioactivity is seen in the posterior mediastinal mass lesion and other sites considered as abnormal findings. In April 2002, the patient underwent surgery. After the excision of the 4.5 3.0 2.5 cm3 tumor in the posterior mediastinum, a bilateral total adrenalectomy was performed. The size of the left adrenal mass (5.2 4.5 3.7 cm3) was much larger than the right adrenal mass (1.0 0.9 0.8 cm3). Microscopically, surgical specimens of the adrenal and posterior mediastinal masses showed typical findings of pheochromocytoma and paraganglioma, respectively (Fig. 1C and D); the two lesions show a similar growth pattern; polygonal cells with sharply defined border are arranged in irregular nests
around a delicate vasculature (Zellballen pattern). Immunohistochemical staining is markedly positive for neuron-specific enolase and chromogranin. There is no finding of malignancy; mitosis is very rare (less than 1 per 30 high power field). Moreover, hemorrhage, necrosis and invasion to surrounding tissue and vessels are not seen. The posterior mediastinal mass was surrounded by normal paraganglion tissues (Fig. 1E); paraganglion tissue including ganglion cells and peripheral nerve bundles around the mass are seen.
Discussion Paragangliomas (extra-adrenal pheochromocytomas) are rare tumors arising from extra-adrenal chromaffin tissues that are derived from the neural crest. The most common site of paragangliomas is the region between the diaphragm and the inferior renal poles and at least 85% of all extra-adrenal pheochromocytomas have been found below the diaphragm.1 Our case is quite rare in that the
ARTICLE IN PRESS 576
patient had a posterior mediastinal paraganglioma and bilateral adrenal pheochromocytoma concurrently. Rare cases of multifocal tumors have been reported in diseases with genetic abnormality. Onethird of multiple endocrine neoplasia (MEN) type 2 or Von Hippel–Lindau disease have been presented as bilateral pheochromocytoma.2 The bilaterality suggests a multicentric origin in the development of these tumors. But, it is extremely rare multifocal tumors in sporadic case like this patient. It is important to investigate the entire body in patients suspecting pheochromocytomas because pheochromocytomas may arise in extra-adrenal locations in about 18% of patients.1 In our patient, we were not able to detect the posterior mediastinal mass earlier because we did not examine the entire body carefully. For this purpose, 131I-MIBG scintigraphy is very useful to detect extra-adrenal disease, especially in the examination of postoperative recurrence or malignant metastatic disease.3,4 The high efficacy of 131I-MIBG scintigraphy for the detection of phechromocytoma is well known. However, there was no uptake of 131I-MIBG in the posterior mediastinal lesion in this case. A false-negative rate of about 10% has been reported.5,6 Although the exact reasons are unknown, the most likely explanation is variability in the spectrum of uptake capacity. 131I-MIBG enters pheochromocytoma cells by two different pathways. Type I amine uptake is a specific, energyrequiring, sodium-dependent and saturable mechanism, which predominates when the concentration of MIBG is less than 10 mM/l. Type II uptake (nonspecific, energy-independent, diffusional mechanism) occurs at higher concentrations.7,8 The uptake of 131I-MIBG is believed to be mainly due to the type I mechanism and subsequent storage in catecholamine-storage granules. On the other hand, it is also possible that a metastatic lesion can have a different scintigraphic quality than the primary tumor. But, we could not find any case reports about the difference in scintigraphic quality between metastatic lesion and primary focus of pheochromocytoma. If a lesion is the true metastatic lesion from the primary tumor, the nature of uptake of radioisotope will be the same because they have the identical histologic features. At first, we had thought that the posterior mediastinal mass might be a metastatic lesion from the adrenal pheochromocytoma. However, we were able to conclude that the thoracic mass was not a
H.J. Kwon et al.
metastatic lesion for the following reasons. First, the surgical specimen of the posterior mediastinal mass showed typical findings of paraganglioma and had no malignant features. Second, the posterior mediastinal mass was surrounded by normal paraganglion tissues. Malignant pheochromocytoma have the feature of extensive local invasion or metastasis to sites where chromaffin tissue is not normally present.9 Third, the 131I-MIBG scintigraphy of the posterior mediastinal mass was negative, unlike the adrenal lesion. In conclusion, paragangliomas can coexist with adrenal pheochromocytomas although the incidence is very rare. Therefore, clinicians who see patients with adrenal pheochromocytomas should investigate the entire body. At this time, 131I-MIBG scintigraphy is very useful for initial examination, but careful attention is required because of the possibility of a false negative.
References 1. Whalen RK, Aithausen AF, Daniels GH. Extra-adrenal pheochromocytoma: review article. J Urol 1992;147: 1–10. 2. Hoffman RW, Gardner DW, Mitchell FL. Intrathoracic and multiple abdominal pheochromocytomas in von Hippel– Lindau disease. Arch Intern Med 1982;142:1962–4. 3. Maurea S, Cuocolo A, Reynolds JC, et al. Iodine-131metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: comparison with CT 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 MR imaging with CT and I-131 MIBG scintigraphy. Radiology 1987;165:89–93. 5. Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, Beierwaltes WH. Iodine-131 metaiodobenzylguanidine for the location of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 1985;26:576–85. 6. Chatal JF, Charbonnel B. Comparison of iodobenzylguanidine imaging with computed tomography in locating pheochromocytoma. 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 metaiodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol 1984;26:539–46. 8. Jacques S, Tobes MC, Sisson JC. Sodium dependency of uptake of norepinephrine and m-iodobenzylguanidine into cultured human 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.