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Japanese Journal of Clinical Oncology Pages 346-349

Pheochromocytoma Growing Exophytically from the Right Adrenal Gland and Invaginating into the Liver
Introduction
Case Report
Discussion
References

Pheochromocytoma Growing Exophytically from the Right Adrenal Gland and Invaginating into the Liver

Pheochromocytoma Growing Exophytically from the Right Adrenal Gland and Invaginating into the Live r Junji Ueda1, Kenichi Takayasu1, Yukio Muramatsu1, Ryouko Iwata1, Tomoo Kosuge2, Michiie Sakamoto3 and Mitsuo Satake4

Departments of 1Diagnostic Radiology and 2Surgery, National Cancer Center Hospital, 3Pathology Division, National Cancer Center Research Institute, Tokyo, and 4Department of Radiology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

A 5-cm pheochromocytoma located in segment 7 of the liver was found incidentally in a 45-year-old man with mild diabetes mellitus and hypertension, and resected. The tumor was demonstrated by computed tomography and magnetic resonance imaging to have completely invaginated itself into the liver and to be receiving blood from a dilated right hepatic artery alone. Surgery revealed the hepatic mass to be tightly adherent to the right adrenal gland. The histopathologic diagnosis was pheochromocytoma growing exophytically from the right adrenal gland. There was no association with multiple endocrine neoplasia type 1 and type 2. A postoperative 131I metaiodobenzylguanidine scan revealed no accumulation, and the patient is currently doing well without recurrence or hypertension one year after the operation. A pheochromocytoma deeply invaginating into the liver should be considered in the differential diagnosis of primary hypervascular hepatic tumors.

Key words: pheochromocytoma - adrenal gland - liver

INTRODUCTION

Pheochromocytoma occurs mainly in the adrenal glands (82-85%), and other cases (15-18%) arising in extra-adrenal locations (1 ,2 ) are known as paraganglioma. Extra-adrenal pheochromocytoma may occur at any location where paraganglion tissue is present; 46% of cases are in the superior para-aortic region (between the diaphragm and the inferior renal poles), 29% in the inferior para-aortic region (between the lower renal poles and the aortic bifurcation), 10% each in the urinary bladder and thorax and the remainder at other sites (2 ).

However, pheochromocytoma located in the liver, known as primary hepatic pheochromocytoma, is very rare and only two cases have been reported up to 1995 (3 ,4 ). We report a case of pheochromocytoma invaginating into the posterior area of the liver, in which the preoperative diagnosis was difficult.

CASE REPORT

A 45-year-old man was referred to our hospital for further examination of a hepatic mass, which was found incidentally by ultrasonography (US) at another hospital. Hypertension and diabetes mellitus were also pointed out, but followed without treatment for about three months.

On admission, blood pressure was 180/110 mm Hg and results of liver function tests were normal. The fasting blood glucose level was 164 mg/dl (normal range 70-110). Hepatitis B surface antigen and hepatitis C virus antibody were negative. Several tumor markers such as alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 showed normal levels. On physical examination, neither lymph nodes nor tumors of the thyroid gland were palpable.

US demonstrated a well defined hyperechoic mass with cystic portions within it. Dynamic CT in the early phase revealed a well enhanced mass 5 cm in diameter located in segment 7 of the liver (Fig. 1 ). In the late phase 5 min later, the mass remained slightly high in density relative to the surrounding liver parenchyma. The mass was hypointense on T1-weighted MR imaging (T1WI) (TR, 600; TE, 15) (Fig. 2 A) and markedly hyperintense on T2WI (TR, 6000; TE, 112) (Fig. 2 B). The right adrenal gland was not confirmed by US, CT or MRI. Subsequent proper hepatic angiography revealed a hypervascular mass fed from the dilated right hepatic artery (Fig. 3 A) and an arterio-portal shunt was seen in the late phase. A right inferior adrenal arteriogram showed the lower half of the adrenal gland with a normal contour, without any feeder to the hepatic mass (Fig. 3 A). The right superior adrenal artery derived from the inferior phrenic artery also showed no feeder to the mass. Thus the mass was fed by the right hepatic artery alone. During angiography, no hypertensive crisis was recognized. Upper and lower gastrointestinal examination revealed no abnormal lesion.


Figure 1. A hypervascular mass with internal cystic components (arrowheads) demonstrated in the liver in the early phase of dynamic CT (A). The atrophic right lobe with arterio-portal shunting (arrows) and a hypertrophic left lobe are clearly divided. In late-phase CT (B) the tumor remains highly dense.

The patient underwent surgery under a suspected diagnosis of primary hepatic carcinoid tumor, atypical focal nodular hyperplasia (FNH), or hepatocellular adenoma.

At laparotomy, mobilization of the right lobe followed by dissection of the liver was contemplated, but the right adrenal gland and the liver tumor adhered too firmly to be separated. During mobilization of the liver, hypertension occurred abruptly and the blood pressure fluctuated. The hepatic mass was therefore strongly suspected to be a pheochromocytoma, and continuity of the adrenal gland with the hepatic mass was confirmed. Therefore, adrenalectomy and right lobectomy were carried out separately.

The cut surface of the resected specimen showed a brown-colored round mass measuring 5.5 × 3.6 cm with several cystic portions within it, most of which was covered by liver parenchyma. The cystic portions showed old hemorrhage. The pseudocapsule surrounding the mass was macroscopically unclear. Microscopically, the tumor cells had small eosinophilic cytoplasm with pleomorphic nuclei and a predominantly small nest pattern of growth with a pseudoglandular pattern in some areas (Fig. 4 A). Intracellular granules positive for Grimelius and chromogranin A staining were recognized; these findings were compatible with pheochromocytoma. Dense fibrous tissue was seen between the mass and the hepatic parenchyma in some parts (Fig. 4 B). The adrenal cortex remained inside the fibrous tissue, i.e., between the pheochromocytoma and liver parenchyma. These findings suggested that the tumor had developed from the cranial portion of the right adrenal gland and invaginated into the liver. Calcification was not confirmed. The non-tumorous portion was normal hepatic parenchyma with congestion and edema. The right adrenal gland was resected separately, and found to be histopathologically normal.


Figure 2. MR images. (A), T1-weighted image shows a hypointense mass with a linear more hypointense structure within it. (B), T2-weighted image shows a markedly hyperintense area. The area right lateral to the mass is slightly hypointense in (A) and hyperintense in (B).

The postoperative course was uneventful and the patient is now doing well without recurrence one year after the operation. His blood pressure has remained normal without administration of anti-hypertensive drugs, and a postoperative 131I metaiodobenzylguanidine (MIBG) scan showed no abnormal accumulation suggestive of recurrence or an extra-adrenal primary lesion.

DISCUSSION


Figure 3. Hepatic arteriogram (A) and right inferior adrenal arteriogram (B). A hypervascular mass with abundant tumor vessels is demonstrated in hepatic segment 7 by hepatic arteriography. However, the right inferior adrenal arteriogram depicts only the lower half of the right adrenal gland.

The mass was demonstrated by both CT (Fig. 2 ) and MRI (Fig. 3 ) to invaginate into the liver, and to be supplied by the dilated right hepatic artery rather than the right adrenal artery. Therefore, it was suspected of being an intrahepatic hypervascular mass with arterio-portal shunt, such as a carcinoid tumor, atypical FNH or adenoma. At the cut surface of the resected specimen, most of the mass was found to be covered by liver parenchyma. During the enlargement of a pheochromocytoma, it may receive blood from surrounding organs, especially the liver. However, a pheochromocytoma derived from the adrenal gland is usually supplied via the adrenal artery.


Figure 4. Histology of the tumor. (A), the tumor is microscopically composed of pheochromocytes which are arranged in small nests and alveolar patterns. Histological diagnosis was pheochromocytoma. (B), Thin adrenal cortical tissue C exists between the pheochromocytoma P and hepatic parenchyma H, with fibrous tissue F.

For a pheochromocytoma located in the liver, primary hepatic pheochromocytoma or metastasis from an extrahepatic malignant pheochromocytoma could be considered. Metastasis occurs in 10-15% of all pheochromocytomas, the liver being second to the skeleton as the most common site for spread (5 ). In the present case, metastasis was ruled out because of the postoperative course and the results of 131I MIBG scanning. Primary hepatic pheochromocytoma is very rare and only two cases have been reported up to 1995 (4 ). Adrenal rest tumor, derived from ectopic adrenocortical cells, is also rare, and only four functional cases have been reported up to 1986 (6 ).

Microscopic study confirmed that the tumor had developed from the cranial portion of the right adrenal gland and subsequently invaginated into the liver; fibrous tissue was recognized between the liver parenchyma and the mass, and adrenal cortical tissue remained between the fibrous tissue and the mass (Fig. 4 B). That is, the fibrous tissue anatomically located between the liver and the adrenal gland and cortical tissue might have been displaced and compressed against the liver by the exophytically growing tumor. Even though this pheochromocytoma had invaded into the liver parenchyma, such a feature does not always indicate high malignancy, and follow-up is needed for confirmation.

As a possible origin of this pheochromocytoma other than the right adrenal gland, a paraganglion located incidentally between the liver and the right adrenal gland, or adreno-hepatic fusion, might be considered, since the parenchymal cells of pheochromocytoma arising from the neural crest can migrate to various locations in autonomic tissue, most commonly the sympathetic ganglia and the organ of Zuckerkandl. Moreover, the incidence of adreno-hepatic fusion is reported to be 9.9% among autopsy cases (7 ). If this tumor had developed in such an area, this may account for its unusual development, i.e., deep invagination into the liver, and its blood supply, i.e., from the right hepatic artery alone, without feeding from the right adrenal artery.

Apart from the location of this tumor, the imaging data were characteristic of pheochromocytoma; hypervascularity on arteriography and CT, hypointensity on T1WI and very bright on T2WI (8 ), although some lesions of edematous or necrotic adrenal metastasis have a similar appearance (9 ). Internal cyst formation was compatible with intratumoral hemorrhage, which is frequently seen in pheochromocytoma. The linear hypointense structures seen on T1WI (Fig. 2 A) were presumed to be dilated tumor vessels.

Arteriography even for suspected pheochromocytoma is contraindicated due to possible hypertensive crisis. However, the present case did not manifest this, because catecholamine produced might have been directly released into the portal vein rather than the hepatic vein, which was shown by dynamic CT (Fig. 1 A) and late arteriography. The catecholamine released into the portal vein may be degraded by hepatocytes. The microscopic changes in the hepatic parenchyma such as congestion and edema, and gross atrophy of the right lobe, might be related to the continuous release of catecholamine into the portal vein. MRI (Fig. 2 ) supported these pathologic changes in the right lobe.

References

1. Moulton JS, Moulton JS. CT of the adrenal glands. Semin Roentgenol 1988;23:288-303. MEDLINE Abstract

2. Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma. J Urol 1992;147:1-10. MEDLINE Abstract

3. Craig JR, Peter RL, Edmondson HA. Tumors of the liver and intrahepatic bile ducts. In: Atlas of Tumor Pathology, 2nd series, fascicle 23. Washington DC: Armed Forces Institute of Pathology, 1989;105-6.

4. Jaeck D, Paris F, Welch M, Stephan D, Chenard-Neu MP, Steib A et al. Primary hepatic pheochromocytoma: a second case. Surgery 1995;117:586-90. MEDLINE Abstract

5. Drain H. Treatment of malignant pheochromocytoma. West J Med 1978;128:106-11.

6. Contreras P, Altieri E, Liberman C, Gac A, Rojas A, Ibarra A et al. Adrenal rest tumor of the liver causing Cushing syndrome: treatment with ketoconazole preceding an apparent surgical cure. J Clin Endocrinol Metab 1985;60:21-8. MEDLINE Abstract

7. Honma K. Adreno-hepatic fusion. An autopsy study. Zentralb Pathol 1991;137:117-22. MEDLINE Abstract

8. Reinig JW, Doppman JL, Dwyer AJ, Frank J. MRI of indeterminate adrenal masses. AJR 1986;147:493-6.

9. Mitchell DG, Crovello M, Matteucci T, Petersen RO, Miettinen MM. Benign adrenocortical masses: diagnosis with chemical shift MR imaging. Radiology 1992;185: 345-51. MEDLINE Abstract

Received January 28, 1997; accepted April 1, 1997
For reprints and all correspondence: Kenichi Takayasu, Department of Diagnostic Radiology, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan
Abbreviations: MRI, magnetic resonance imaging; US, ultrasonography; T1WI, T1-weighted MRI; T2WI, T2-weighted MRI; FNH, focal nodular hyperplasia; MIBG, metaiodobenzylguanidine.

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