216
CLINICAL IMAGING 1991;15:216-219
NONFUNCTIONAL OF THE LIVER
PARAGANGLIOMA
YOUNG S. KANG, MD, JANET E. KUHLMAN, MD, ELLIOT K. FISHMAN, MD AND ELIAS A. ZERHOUNI,
Paragangliomas occurring in the liver are rare. We report a patient with a history of nonfunctional paragangliomas in the head and neck who developed liver metastases years later. We discuss findings on cross-sectional imaging modalities, including magnetic resonance imaging (MRI), which demonstrate the hypervascular nature of the liver masses. KEY WORDS:
Paraganglioma; Glomus tumor; Metastasis; Magnetic resonance imaging (MRI)
Liver:
Paragangliomas are rare neoplasms arising from neural crest-cell derivatives located adjacent to sympathetic ganglia and plexuses throughout the body. The subset of these tumors secreting excess catecholamines are termed pheochromocytomas, which originate most often in the adrenal medulla. The majority of extraadrenal paragangliomas are nonfunctional, and are most commonly located in the head and neck, retroperitoneum, and mediastinum. Nonfunctional paragangliomas are slow-growing and usually benign, but can be locally invasive and recur if incompletely excised. Distant metastases are uncommon, but spread to the bone and lungs is welldocumented (1). Several cases of nonfunctional paragangliomas metastatic to the liver exist in the
From The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore. Marvland. Address reprint requests to: Janet Kuhlman, M.D., Department of Radiology, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21205. Received October 10, 1990. 8 1991 by Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0899-7071/91/$3.50
MD
clinical and pathological literature (l-3), but radiologic features of the liver lesions have not been described. We report a case of a metastatic paraganglioma in a patient who presented with multiple liver masses. CASE REPORT A %-year-old black woman was referred to our institution because several masses were discovered in the liver on ultrasound during an evaluation of chronic anemia. Her past medical history was significant for resection of a right glomus jugulare at age 17, and a left carotid body tumor at age 27. At presentation she complained only of mild abdominal pain. A physical examination revealed a right upper quadrant bruit. Laboratory values were remarkable only for hemoglobin of 7.9 g/dl; urinary catecholamines were negative. A Tc-labeled red blood cell (RBC) scan showed a large area of mildly decreased tracer accumulation in the left lobe of the liver (Figure 1); the appearance was not consistent with that of a hemangioma. A biopsy of the left lobe mass was performed under ultrasound guidance; the mass appeared to be echopenic (Figure 2) with a small punctate echogenic focus at the periphery. The biopsy was nondiagnostic. Computed tomography (CT) with intravenous contrast showed a 5 x 4 cm mass of low attenuation in the left lobe of the liver (Figure 3), and two other smaller lesions in the right lobe with a few scattered small calcifications. Magnetic resonance imaging (MRI) was then performed at 1.5 T (Figure 4). The focal liver lesions seen on CT were clearly demonstrated. All had low signal intensity on Tl-weighted images, and slightly increased signal on T2-weighted images relative to the rest of the liver parenchyma. In addition, marked enlargement of vessels including the main hepatic artery was seen with areas of
JULY-SEPTEMBER
NONFUNCTIONAL
1991
PARAGANGLIOMA
OF THE LIVER
217
FIGURE 2. A large hypoechoic mass (arrows) on a trans-
verse view of the left lobe of the liver on ultrasound.
I FIGURE 1. A Tc-labeled RBC scan shows an area of mini-
mally decreased tracer accumulation in the left lobe of the liver (arrows).
neovascularity at the periphery of the left lobe lesion. Multiple punctate and linear areas of signal void due to vessels within the masses were also seen. The patient underwent laparoscopically guided biopsy of the left lobe lesion. The pathological diagnosis was a paraganglioma, with histological features similar to those of her original carotid body tumor. The patient was referred to radiation therapy. DISCUSSION A clinically important classification of paragangliomas is dependent on their being functional. Positive staining of the tumor specimen for chromaffin has not correlated consistently with the endocrine func-
tion; rather, the 2$-hr urine test for catecholamines remains the most reliable test. The radiologic workup of a patient with clinical or endocrine evidence of a functioning paraganglioma, or pheochromocytoma, is by now well-established: initial adrenal imaging with CT or MB, may be followed by a (MIBG) whole-body I-131 metaiodobenzylguanidine scan; if necessary, scintigraphy-guided selective anatomic imaging -is then performed (4). A nonfunctional paraganglioma, on the other hand, is usually
FIGURE 3. A mass of decreased attenuation (arrows) is seen in the left lobe of the liver on contrast-enhanced CT.
218
KANG ET AL,
CLINICAL IMAGING VOL. 15, NO. 3
B FIGURE 4. MRI of the liver at 1.5 T. (A) Tl-weighted im-
age (TR/TE = 600/20) shows a large left lobe mass with decreased signal intensity. (B) Tl-weighted image at the level of the celic axis shows marked enlargement of the main hepatic artery (arrow) and its proximal branches, as well as proliferation of tortuous smaller vessels compatible with neovascularity. Two lesions in the right lobe are also seen. (C) T2-weighted image (TR/TE = 2200/80) at the level of the left lobe mass. The lesion is slightly more intense than the surrounding parenchyma. Signal void due to increased vasculature at the posterior border of the mass, and punctate and linear vessels within the mass are seen.
discovered during evaluation of local symptoms, and traditionally search for occult metastases has not been required. The incidence of metastasis from paragangliomas varies in the literature, and appears to depend on the primary site. The frequency was 12% in a large series on carotid body tumors (5), whereas it ranged 28% to 38% if the primary tumor was in the organ of Zuckerkandl (6). The most frequent metastatic sites are bone, the spine in particular, the lung, and the regional nodes. Two themes seem to recur regarding metastatic paragangliomas. First, although Lack et al. (7) have described histologic criteria of malignancy, it is now considered difficult to determine metastatic potential of the primary tumor based on histology alone, even in retrospect. Second, metastatic foci are
discovered typically years after apparent successful treatment of the initial tumor. Several cases of nonfunctional paragangliomas metastatic to the liver have been documented from carotid body tumors and from primary retroperitoneal sites. In addition, paragangliomas of the intrahepatic bile duct (8) and of the falciform ligament (9), possibly representing novel primary sites, have been reported. These reports, however, have not described radiographic features of nonfunctional paragangliomas of the liver. In our case, findings on tagged RBC scan, ultrasound, and CT were largely nonspecific: diminished uptake of the tracer, decreased echogenicity, and low attenuation, respectively, of the lesion relative to the rest of the liver parenchyma. The MR signal characteristics of the lesions were fairly nonspecific: very long T2 frequently associated with pheochromocytomas was not a feature of the lesion in this case. A striking MR finding, however, was the demonstration of a markedly enlarged hepatic artery, neovascularity at the periphery of the mass, and multiple punctate vessels within the
JULY-SEPTEMBER 1991
mass, indicating a highly vascular nature of the lesion. Interestingly, in paragangliomas of the head and neck, multiple small areas of signal void due to blood flow are also often noted in the matrix of the tumor on MR (10). Just as in the evaluation of head and neck paragangliomas, if the liver lesions are deemed unresectable, MR may be sufficient, and obviate the need for angiography. The MR demonstration of vascular enlargement and proliferation in liver metastases of a nonfunctional paraganglioma, a feature often seen in the primary tumor, illustrates one of the advantages of MR in the evaluation of focal hepatic masses.
REFERENCES 1. Rangwala AF, Sylvia LC, Becker SM. Soft tissue metastasis of a chemodectoma: A case report and review of the literature. Cancer 1978; 42:2865-2869.
NONFUNCTIONAL PARAGANGLIOMA
OF THE LIVER
219
2. Olson JR, Abel1 MR. Nonfunctional, nonchromaffin paragangliomas of the retroperitoneum. Cancer 1969; 23:1358-1367. 3. Aviram R, Mor C, Reiss R. Simultaneous local recurrence of retroperitoneal paraganglioma with liver metastases. Arch Path01 Lab Med 1985; 109:373-374. 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. Zbaren P, Lehmann W. Carotid body paraganglioma with metastases. Laryngoscope 1985; 95:450-454. 6. Glenner GG, Grimley PM. Tumors of the extra-adrenal paraganglion system (including chemoreceptors). Atlas of Tumor Pathology, Washington DC: Armed Forces Institute of Pathology 1974;13-86. 7. Lack EE, Cubilla AL, Woodruff JM. Paragangliomas of the head and neck region: A pathologic study of tumors from 71 patients. Hum Path01 1979; 10:191-218. 8. Sarma DP, Rodriguez H Jr, Hoffmann EO. Paraganglioma of the hepatic duct. Southern Med J 1980; 73:1677-1678. 9. Delbridge L, Connolly J. Paraganglioma of the falciform ligament: A case report. Aust N Z J Surg 1982; 52:315-317. 10. Olsen WL, Dillon WP, Kelley WM, Norman D, Brant-Zawadzki M, Newton TH. MR imaging of paragangliomas. AJNR 1986; 7:1039-1042.
CLINICAL IMAGING 1991;15:216-219
NONFUNCTIONAL OF THE LIVER
PARAGANGLIOMA
YOUNG S. KANG, MD, JANET E. KUHLMAN, MD, ELLIOT K. FISHMAN, MD AND ELIAS A. ZERHOUNI,
Paragangliomas occurring in the liver are rare. We report a patient with a history of nonfunctional paragangliomas in the head and neck who developed liver metastases years later. We discuss findings on cross-sectional imaging modalities, including magnetic resonance imaging (MRI), which demonstrate the hypervascular nature of the liver masses. KEY WORDS:
Paraganglioma; Glomus tumor; Metastasis; Magnetic resonance imaging (MRI)
Liver:
Paragangliomas are rare neoplasms arising from neural crest-cell derivatives located adjacent to sympathetic ganglia and plexuses throughout the body. The subset of these tumors secreting excess catecholamines are termed pheochromocytomas, which originate most often in the adrenal medulla. The majority of extraadrenal paragangliomas are nonfunctional, and are most commonly located in the head and neck, retroperitoneum, and mediastinum. Nonfunctional paragangliomas are slow-growing and usually benign, but can be locally invasive and recur if incompletely excised. Distant metastases are uncommon, but spread to the bone and lungs is welldocumented (1). Several cases of nonfunctional paragangliomas metastatic to the liver exist in the
From The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore. Marvland. Address reprint requests to: Janet Kuhlman, M.D., Department of Radiology, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21205. Received October 10, 1990. 8 1991 by Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0899-7071/91/$3.50
MD
clinical and pathological literature (l-3), but radiologic features of the liver lesions have not been described. We report a case of a metastatic paraganglioma in a patient who presented with multiple liver masses. CASE REPORT A %-year-old black woman was referred to our institution because several masses were discovered in the liver on ultrasound during an evaluation of chronic anemia. Her past medical history was significant for resection of a right glomus jugulare at age 17, and a left carotid body tumor at age 27. At presentation she complained only of mild abdominal pain. A physical examination revealed a right upper quadrant bruit. Laboratory values were remarkable only for hemoglobin of 7.9 g/dl; urinary catecholamines were negative. A Tc-labeled red blood cell (RBC) scan showed a large area of mildly decreased tracer accumulation in the left lobe of the liver (Figure 1); the appearance was not consistent with that of a hemangioma. A biopsy of the left lobe mass was performed under ultrasound guidance; the mass appeared to be echopenic (Figure 2) with a small punctate echogenic focus at the periphery. The biopsy was nondiagnostic. Computed tomography (CT) with intravenous contrast showed a 5 x 4 cm mass of low attenuation in the left lobe of the liver (Figure 3), and two other smaller lesions in the right lobe with a few scattered small calcifications. Magnetic resonance imaging (MRI) was then performed at 1.5 T (Figure 4). The focal liver lesions seen on CT were clearly demonstrated. All had low signal intensity on Tl-weighted images, and slightly increased signal on T2-weighted images relative to the rest of the liver parenchyma. In addition, marked enlargement of vessels including the main hepatic artery was seen with areas of
JULY-SEPTEMBER
NONFUNCTIONAL
1991
PARAGANGLIOMA
OF THE LIVER
217
FIGURE 2. A large hypoechoic mass (arrows) on a trans-
verse view of the left lobe of the liver on ultrasound.
I FIGURE 1. A Tc-labeled RBC scan shows an area of mini-
mally decreased tracer accumulation in the left lobe of the liver (arrows).
neovascularity at the periphery of the left lobe lesion. Multiple punctate and linear areas of signal void due to vessels within the masses were also seen. The patient underwent laparoscopically guided biopsy of the left lobe lesion. The pathological diagnosis was a paraganglioma, with histological features similar to those of her original carotid body tumor. The patient was referred to radiation therapy. DISCUSSION A clinically important classification of paragangliomas is dependent on their being functional. Positive staining of the tumor specimen for chromaffin has not correlated consistently with the endocrine func-
tion; rather, the 2$-hr urine test for catecholamines remains the most reliable test. The radiologic workup of a patient with clinical or endocrine evidence of a functioning paraganglioma, or pheochromocytoma, is by now well-established: initial adrenal imaging with CT or MB, may be followed by a (MIBG) whole-body I-131 metaiodobenzylguanidine scan; if necessary, scintigraphy-guided selective anatomic imaging -is then performed (4). A nonfunctional paraganglioma, on the other hand, is usually
FIGURE 3. A mass of decreased attenuation (arrows) is seen in the left lobe of the liver on contrast-enhanced CT.
218
KANG ET AL,
CLINICAL IMAGING VOL. 15, NO. 3
B FIGURE 4. MRI of the liver at 1.5 T. (A) Tl-weighted im-
age (TR/TE = 600/20) shows a large left lobe mass with decreased signal intensity. (B) Tl-weighted image at the level of the celic axis shows marked enlargement of the main hepatic artery (arrow) and its proximal branches, as well as proliferation of tortuous smaller vessels compatible with neovascularity. Two lesions in the right lobe are also seen. (C) T2-weighted image (TR/TE = 2200/80) at the level of the left lobe mass. The lesion is slightly more intense than the surrounding parenchyma. Signal void due to increased vasculature at the posterior border of the mass, and punctate and linear vessels within the mass are seen.
discovered during evaluation of local symptoms, and traditionally search for occult metastases has not been required. The incidence of metastasis from paragangliomas varies in the literature, and appears to depend on the primary site. The frequency was 12% in a large series on carotid body tumors (5), whereas it ranged 28% to 38% if the primary tumor was in the organ of Zuckerkandl (6). The most frequent metastatic sites are bone, the spine in particular, the lung, and the regional nodes. Two themes seem to recur regarding metastatic paragangliomas. First, although Lack et al. (7) have described histologic criteria of malignancy, it is now considered difficult to determine metastatic potential of the primary tumor based on histology alone, even in retrospect. Second, metastatic foci are
discovered typically years after apparent successful treatment of the initial tumor. Several cases of nonfunctional paragangliomas metastatic to the liver have been documented from carotid body tumors and from primary retroperitoneal sites. In addition, paragangliomas of the intrahepatic bile duct (8) and of the falciform ligament (9), possibly representing novel primary sites, have been reported. These reports, however, have not described radiographic features of nonfunctional paragangliomas of the liver. In our case, findings on tagged RBC scan, ultrasound, and CT were largely nonspecific: diminished uptake of the tracer, decreased echogenicity, and low attenuation, respectively, of the lesion relative to the rest of the liver parenchyma. The MR signal characteristics of the lesions were fairly nonspecific: very long T2 frequently associated with pheochromocytomas was not a feature of the lesion in this case. A striking MR finding, however, was the demonstration of a markedly enlarged hepatic artery, neovascularity at the periphery of the mass, and multiple punctate vessels within the
JULY-SEPTEMBER 1991
mass, indicating a highly vascular nature of the lesion. Interestingly, in paragangliomas of the head and neck, multiple small areas of signal void due to blood flow are also often noted in the matrix of the tumor on MR (10). Just as in the evaluation of head and neck paragangliomas, if the liver lesions are deemed unresectable, MR may be sufficient, and obviate the need for angiography. The MR demonstration of vascular enlargement and proliferation in liver metastases of a nonfunctional paraganglioma, a feature often seen in the primary tumor, illustrates one of the advantages of MR in the evaluation of focal hepatic masses.
REFERENCES 1. Rangwala AF, Sylvia LC, Becker SM. Soft tissue metastasis of a chemodectoma: A case report and review of the literature. Cancer 1978; 42:2865-2869.
NONFUNCTIONAL PARAGANGLIOMA
OF THE LIVER
219
2. Olson JR, Abel1 MR. Nonfunctional, nonchromaffin paragangliomas of the retroperitoneum. Cancer 1969; 23:1358-1367. 3. Aviram R, Mor C, Reiss R. Simultaneous local recurrence of retroperitoneal paraganglioma with liver metastases. Arch Path01 Lab Med 1985; 109:373-374. 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. Zbaren P, Lehmann W. Carotid body paraganglioma with metastases. Laryngoscope 1985; 95:450-454. 6. Glenner GG, Grimley PM. Tumors of the extra-adrenal paraganglion system (including chemoreceptors). Atlas of Tumor Pathology, Washington DC: Armed Forces Institute of Pathology 1974;13-86. 7. Lack EE, Cubilla AL, Woodruff JM. Paragangliomas of the head and neck region: A pathologic study of tumors from 71 patients. Hum Path01 1979; 10:191-218. 8. Sarma DP, Rodriguez H Jr, Hoffmann EO. Paraganglioma of the hepatic duct. Southern Med J 1980; 73:1677-1678. 9. Delbridge L, Connolly J. Paraganglioma of the falciform ligament: A case report. Aust N Z J Surg 1982; 52:315-317. 10. Olsen WL, Dillon WP, Kelley WM, Norman D, Brant-Zawadzki M, Newton TH. MR imaging of paragangliomas. AJNR 1986; 7:1039-1042.
