British Journal of Radiology 75 (2002),548-551 © 2002 The British Institute of Radiology
False positive uptake of metaiodobenzylguanidine in hepatocellular carcinoma
Y Inoue, MD1,
M Akahane, MD1,
T Kitazawa, MD2,
H Ijichi, MD2,
S Obi, MD2,
K Yoshikawa, MD1,
K Ohtomo, MD3 and
M Omata, MD2
1 Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 and Departments of 2 Gastroenterology and 3 Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
 |
Abstract
|
|---|
We present the case of a patient who showed increased accumulation of 123I-metaiodobenzylguanidine (MIBG) in hepatocellular carcinoma, leading to a false presumptive diagnosis of intrahepatic neuroendocrine tumour. The increase in uptake was not seen on images obtained 4 h after tracer injection but was evident on those taken after 24 h, suggesting slower washout from the liver tumour than from non-tumoural liver parenchyma. Our observations indicate that a non-neuroendocrine malignant tumour may exhibit high accumulation of MIBG associated with prolonged retention.
|
Introduction
|
|---|
Metaiodobenzylguanidine (MIBG), an analogue of the adrenergic blocking agent guanethidine [1], accumulates in various neuroendocrine tumours originating from the neural crest. Radiolabelled MIBG is accepted as an excellent agent for localizing pheochromocytoma [2, 3] and neuroblastoma [4], and may also be helpful in evaluating medullary thyroid carcinoma [5] and carcinoid tumour [6]. The major advantages of MIBG scanning derive from its very high specificity for neuroendocrine tumours in addition to its facility in whole body assessment [2, 3]. False positive results, i.e. accumulation in lesions other than neuroendocrine tumours, are rarely seen. We describe a patient in whom MIBG scanning was performed to evaluate the cause of hypertension and in whom increased uptake was observed in hepatocellular carcinoma.
|
Case report
|
|---|
A 72-year-old man was referred for 123I-MIBG scintigraphy to exclude pheochromocytoma as a cause of refractory hypertension. He had severe hypertension that was poorly controlled with antihypertensive drugs, and secondary hypertension was suspected. Pheochromocytoma was taken into consideration, although he did not suffer from other symptoms suggestive of the diagnosis such as headache, palpitation and sweating.
He received 111 MBq (3 mCi) of 123I-MIBG, and whole body anterior and posterior images were acquired 4 h later. Anterior and posterior spot views of the chest and abdomen were also collected 4 h and 24 h post injection. Photopenic areas were observed in the liver at 4 h after tracer injection (Figure 1
). The 24 h post injection images, in turn, demonstrated inhomogeneously increased uptake in the liver, around the photopenic areas seen at 4 h (Figure 2). No abnormal uptake was detected elsewhere. Based on the findings of 123I-MIBG scan, intrahepatic neuroendocrine tumour, including hepatic metastasis from primary unknown pheochromocytoma and primary hepatic pheochromocytoma, was suspected.
View larger version (174K):
[in this window]
[in a new window]
|
Figure 1. Anterior abdominal image obtained 4 h postinjection of 123I-metaiodobenzylguanidine. Photopenic areas are seen in the liver.
|
|
View larger version (175K):
[in this window]
[in a new window]
|
Figure 2. Anterior abdominal view obtained 24 h post injection of 123I-metaiodobenzylguanidine. Inhomogeneously increased uptake is noted in the liver.
|
|
CT of the liver (Figure 3) showed a mass lesion of 13 cm diameter in the right hepatic lobe and a mass of 8 cm diameter in the left medial segment, corresponding to the inhomogeneously increased accumulation of MIBG. Small nodules were also detected in the liver. The lesions in the liver were of low density on pre-contrast images and showed significant enhancement during the arterial phase after the rapid injection of contrast agent. Portal venous phase CT images demonstrated the mass lesions as low density areas surrounded by thin hyperdense rims. A mosaic appearance, namely the presentation of multiple nodular areas of differing CT attenuation within a mass, was noted. These CT findings strongly suggested hepatocellular carcinoma.
View larger version (107K):
[in this window]
[in a new window]
|
Figure 3. CT of the upper abdomen imaged during the portal venous phase after contrast medium injection. A large mass lesion is demonstrated in the liver.
|
|
Serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA-II) were definitely elevated at 13 140 ng ml-1 (normal range <15 ng ml-1) and 35 496 mAU ml-1 (normal range <40 mAU ml-1), respectively, which supported the diagnosis of hepatocellular carcinoma. While mildly elevated plasma noradrenaline of 534 pg ml-1 was noted (normal range 90–420 pg ml-1), estimates of plasma adrenaline, plasma dopamine, urinary adrenaline, urinary noradrenaline, urinary dopamine and urinary vanyllymandelic acid were normal, and biochemical data did not suggest the presence of pheochromocytoma. Serum carcinoembryonic antigen, serum calcitonin and urinary 5-hydroxyindoleacetic acid, measured to assess the possibility of medullary thyroid cancer or carcinoid, showed normal results. Biopsy of the liver tumour was performed, and histopathology proved hepatocellular carcinoma of Edmonson type II. Because multiple tumours, including a large one, were distributed in both hepatic lobes, the patient underwent transcatheter arterial embolisation for hepatic lesions, resulting in decreases in serum AFP and PIVKA-II to 5676 ng ml-1 and 14 433 mAU ml-1, respectively.
|
Discussion
|
|---|
MIBG scanning has been established as useful for the localization of pheochromocytoma. Pheochromocytoma produces catecholamines and may induce symptoms of hypercatecholaminemia. However, there are many causes of hypercatechol aminemia in addition to pheochromocytoma, and conversely, many pheochromocytomas secrete catecholamines into the systemic circulation only periodically. In addition, there is silent or asymptomatic pheochromocytoma as one of the entities presenting as an adrenal incidentaloma [7]. Diagnosing pheochromocytoma is sometimes problematic, and screening with MIBG scanning may be indicated even in the absence of typical clinical and biochemical evidence of pheochromocytoma [8].
MIBG accumulation is seen almost exclusively in neuroendocrine tumours, and reports of increased uptake in other lesions are limited. One major category of false positive MIBG scans is that caused by urinary retention [9]. MIBG is excreted in the urine, and tracer retained in the urinary collecting system may mimic abnormally increased adrenal uptake. This type of false positive scan can be differentiated from a true positive scan relatively easily if physicians keep in mind urinary retention as a possible cause of false positive results. Comparison with other imaging techniques, including renal scintigraphy and/or the administration of a diuretic, would help to avoid misdiagnosis [9]. Other causes of false accumulation of MIBG have been reviewed by Sone et al [10] and Leung et al [11], and include adrenocortical adenoma, adenomatous polyp of the cecum, infantile myofibromatosis, pancreaticoblastoma, acute focal pyelonephritis, hepatic hemangioma and adrenal metastasis of choriocarcinoma. False positive uptake has also been reported in juvenile capillary hemangioma [12] and adrenocortical carcinoma [13].
In the patient described here, MIBG scanning was performed to assess the cause of refractory hypertension, and it showed increased accumulation in the liver. Metastatic liver tumour from neuroendocrine tumour was suspected, although a primary site was not revealed on the MIBG scan. Although pheochromocytoma generally originates from adrenal medulla or the sympathetic nerve system, primary hepatic pheochromocytoma [14] has also been reported and was considered to be a possibility in this patient. However, laboratory data and CT suggested hepatocellular carcinoma, and the histopathologic examination confirmed the diagnosis. Our observation indicates that false positive hepatic accumulation of MIBG may occur in malignant neoplasms not derived from the neural crest.
The accumulation of MIBG depends on two different mechanisms, type 1 and type 2 uptakes, in addition to delivery by blood flow [15]. Type 1 uptake is an energy dependent, saturable process that causes accumulation specific to sympathetic tissue. On the other hand, type 2 uptake is a passive, diffusional process that causes non-specific accumulation in various tissues. Non-specific uptake that forms background activity on MIBG images tends to clear more rapidly than specific uptake [11], resulting in better visualization of neuroendocrine tumours [2, 16, 17] and normal adrenal glands [16, 18] during the later phase after injection of MIBG. Mechanisms of uptake in non-neuroendocrine tumours are unclear, but high tumour dependent blood flow and non-specific diffusional uptake have been postulated as possible causes [11, 19]. The clear delineation in early imaging combined with obscuration in late imaging observed previously [19] appears to be successfully explained by the postulated mechanisms. However, in the patient illustrated here, increased uptake corresponding to the hepatic tumours became evident on the late images, indicating slower washout from the lesions than from the surrounding liver parenchyma. Although an increase in lesion-to-background contrast with time commonly indicates a true positive finding, it is suggested that some non-neuroendocrine tumours exhibit prolonged retention of MIBG and mimic a neuroendocrine tumour even in view of temporal changes in accumulation.
Our observation demonstrates that increased hepatic uptake of MIBG associated with prolonged retention may occur in lesions other than neuroendocrine tumours. The sole basis for considering the presence of pheochromocytoma prior to MIBG scanning in the patient reported here was poorly controlled hypertension. Although MIBG scanning has high specificity for neuroendocrine tumours, its positive predictive value should decrease in patients who have low pre-test likelihoods of neuroendocrine tumours. Detailed endocrinological evaluation is a prerequisite to determining the indication and interpretation of MIBG scanning, and care should be taken in making a diagnosis of silent or asymptomatic pheochromocytoma.
Received for publication January 2, 2002.
Accepted for publication February 14, 2002.
|
References
|
|---|
- Wieland DM, Wu J, Brouwn LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med 1980;21:349–53.[Abstract/Free Full Text]
- Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, Beierwaltes WH. Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 1985;26:576–85.[Abstract/Free Full Text]
- Chatal JF, Charbonnel B. Comparison of iodobenzylguanidine imaging with computed tomography in locating pheochromocytoma. J Clin Endocrinol Metab 1985;61:769–72.[Abstract/Free Full Text]
- Hoefnagel CA, Voute PA, de Kraker J, Marcuse HR. Radionuclide diagnosis and therapy of neural crest tumors using iodine-131 metaiodobenzylguanidine. J Nucl Med 1987;28:308–14.[Abstract/Free Full Text]
- Endo K, Shiomi K, Kasagi K, Konishi J, Torizuka K, Nakao K, et al. Imaging of medullary thyroid cancer with 131I-MIBG. Lancet 1984;2:233.
- Fischer M, Kamanabroo D, Sonderkamp H, Proske T. Scintigraphic imaging of carcinoid tumours with 131I-metaiobenzylguanidine. Lancet 1984;2:165.
- Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, et al. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab 2000;85:637–44.[Abstract/Free Full Text]
- Mozley PD, Kim CK, Mohsin J, Jatlow A, Gosfield E III, Alavi A. The efficacy of iodine-123-MIBG as a screening test for pheochromocytoma. J Nucl Med 1994;35:1138–44.[Abstract/Free Full Text]
- Kao PF, Tzen KY, Huang MJ, You DL. Obstructive hydronephrosis with I-131 MIBG accumulation mimicking huge pheochromocytoma: a diagnostic pitfall found with Tc-99m MDP imaging. Clin Nucl Med 1996;21:994–5.[Medline]
- Sone H, Okuda Y, Nakamura Y, Ishikawa N, Yamaoka T, Kawakami Y, et al. Radioiodinated metaiodobenzylguanidine scintigraphy for pheochromocytoma. A false-positive case of adrenocortical adenoma and literature review. Horm Res 1996;46:138–42.[Medline]
- Leung A, Shapiro B, Hattner R, Kim E, de Kraker J, Ghazzar N, et al. Specificity of radioiodinated MIBG for neural crest tumors in childhood. J Nucl Med 1997;38:1352–7.[Abstract/Free Full Text]
- Frappaz D, Giammarile F, Thiesse P, Ranchere-Vince D, Louis D, Guibaud L, et al. False positive MIBG scan. Med Pediatr Oncol 1997;29:589–92.[Medline]
- Rainis T, Ben-Haim S, Dickstein G. False positive metaiodobenzylguanidine scan in a patient with a huge adrenocortical carcinoma. J Clin Endocrinol Metab 2000;85:5–7.[Abstract/Free Full Text]
- Rimmelin A, Hartheiser M, Gangi A, Welsch M, Jeung MY, Jaeck D, et al. Primary hepatic pheochromocytoma. Eur Radiol 1996;6:82–5.[Medline]
- Shapiro B, Gross MD. Radiochemistry, biochemistry, and kinetics of 131I-metaiodobenzylguanidine (MIBG) and 123I-MIBG: clinical implications of the use of 123I-MIBG. Med Pediatr Oncol 1987;15:170–7.[Medline]
- Paltiel HJ, Gelfand MJ, Elgazzar AH, Washburn LC, Harris RE, Masters PR, et al. Neural crest tumors: I-123 MIBG imaging in children. Radiology 1994;190:117–21.[Abstract/Free Full Text]
- Roelants V, Goulios C, Beckers C, Jamar F. Iodine-131-MIBG scintigraphy in adults: interpretation revisited? J Nucl Med 1998;39:1007–12.[Abstract/Free Full Text]
- Nakajo M, Shapiro B, Copp J, Kalff V, Gross MD, Sisson JC, et al. The normal and abnormal distribution of the adrenomedullary imaging agent m-[I-131]iodobenzylguanidine (I-131 MIBG) in man: evaluation by scintigraphy. J Nucl Med 1983;24:672–82.[Abstract/Free Full Text]
- Stewart RE, Grossman DM, Shulkin BL, Shapiro B. Iodine-131 metaiodobenzylguanidine uptake in infantile myofibromatosis. Clin Nucl Med 1989;14:344–6.[Medline]
Top
Abstract
Introduction
