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Sao Paulo Med J
Sao Paulo Med J
Sao Paulo Med J
São Paulo Medical Journal
1516-3180
1806-9460
Associação Paulista de Medicina - APM

11276173
10.1590/S1516-31802001000200010
Case Report
Multicentric pheochromocytoma and involvement of the inferior vena cava
Lucon Antonio Marmo *
Falci Renato Júnior *
Praxedes José Nery *
Machado Marcel Cerqueira Cesar *
Saldanha Luis Balthazar *
Machado Marcelo Marcondes *
Arap Sami *
Address for correspondence: Antonio Marmo Lucon Divisão de Clínica Urológica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Av. Dr. Eneas de Carvalho Aguiar, 255 7o andar - sala 710 F São Paulo/SP – Brazil - CEP 05403-900 E-mail: webmaster@urologia.hcnet.usp.br
Conflict of interest: Not declared

02 3 2001
2001
119 2 8688
22 9 2000
30 10 2000
https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons license.
ABSTRACT

CONTEXT:

Extension of pheochromocytomas to the inferior vena cava is rare. Multicentric tumors are rare as well, being present in up to 10% of cases. Surgery is the treatment of choice because of the longterm survival free of disease.

DESIGN:

Case report.

CASE REPORT:

We report on a case of right adrenal pheochromocytoma with extension to the supradiaphragmatic vena cava, which underwent surgical excision through thoracophrenic laparotomy without the need for cardiopulmonary bypass. In a 6-year follow-up, another pheochromocytoma was found in the infra-renal Zuckerkandl's organ. Complete surgical excision of the tumor was performed by a median laparotomy and complete retroperitoneal dissection. In both cases, the total removal of the pheochromocytoma has been guaranteed by having margins free of tumor and a normal postoperative level of catecholamines. The pathological study revealed a malignant pheochromocytoma with margins free of neoplasia in both specimens.

RESUMO

CONTEXTO:

Feocromocitoma com invasão de veia cava inferior é raro. Tumores multicêntricos são igualmente raros, estando presentes em até 10% dos casos. A cirurgia é o tratamento de escolha, uma vez que a sobrevida livre da doença é longa.

TIPO DE ESTUDO: Relato de caso.

RELATO DE CASO: Relatamos um caso de feocromocitoma de adrenal direita com extensão para veia cava inferior supra-diafragmática, retirado cirúrgicamente através de tóraco-freno-laparotomia, sem a necessidade de circulação extra-corpórea. Após seis anos de seguimento, outro feocromocitoma foi achado no órgão de Zuckerkandl. A excisão cirúrgica completa do tumor foi realizada através de laparotomia mediana e dissecção retroperitoneal. Em ambos os casos, margens cirúrgicas livres do tumor e níveis pós-operatórios normais de catecolaminas garantiram remoção total do feocromocitoma. O estudo anatomopatológico revelou feocromocitoma maligno com margens livres de neoplasia em ambos os espécimes.

KEY WORDS:

Pheochromocytoma
Retroperitoneal neoplasia
Adrenal tumor
Adrenal surgery
Vena cava
PALAVRAS-CHAVE:

Feocromocitoma
Neoplasia retroperitoneal
Tumor adrenal
Veia cava
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pmcINTRODUCTION

Pheochromocytomas are tumors that arise in the adrenal medulla or in other foci of chromaffin cells and most of them are benign. Some 10% of pheochromocytomas are extra-adrenal, the majority of them being found throughout the length of the sympathetic cell chain, which contains chromaffin cells, whether in the head, the neck, the thorax or the abdomen. The most common site of extra-adrenal pheochromocytoma is Zuckerkandl's organ.1 The excessive secretion of catecholamines by the tumor is responsible for most of the adrenergic signs and symptoms such as hypertension, headache and tachycardia, among others.

Although pheochromocytomas are rarely a cause of hypertension (less than 1% of the hypertensive population), their diagnosis is important by virtue of the potential cure of the hypertension which it represents, and also because of the oncological character of the lesion.2 The available literature reports only 16 cases of this tumor with invasion of the inferior vena cava.3-18 When two or more tumors are found in a patient, the possibility of a family disease as well as multiple endocrine neoplasia should be investigated. The family pheochromocytoma may also be associated with Von Hippel Lindau and Von Recklinghausen's disease.19

Our purpose is to report a case of malignant right adrenal pheochromocytoma with vena cava invasion and its surgical approach.

CASE REPORT

A 43-year-old man was admitted for investigation of recent hypertension onset associated with headache and tremors. Urinary vanillimandelic acid (VMA) was 16 mg/24h (normal range 2 to 12 mg/24h) and the urinary methanephrines were 2.1 mcg/mg of creatinine (normal ranges 0.05 to 1.2). Abdominal ultrasonography showed a solid lesion measuring 6.0 × 6.5 cm in the topography of the right adrenal. A computerized tomography (CT) scan confirmed the ultrasonography findings and revealed its extension into the inferior vena cava above the diaphragm without reaching the right atrium.

A right thoracophrenic laparotomy allowed good access to the tumor and inferior vena cava. First, the supra-diaphragmatic inferior vena cava was dissected and repaired. The same procedure was used to control the left renal vein and inferior vena cava below the renal vein. The tumor and the right kidney were isolated and removal en bloc was performed, preserving the right adrenal vein with its tumoral thrombi inside. Vascular clamps were then placed on the infra-renal vena cava, left renal vein, hepatic pedicle (Pringle's maneuver) and intra-thoracic inferior vena cava. The anterior wall of the abdominal vena cava was opened and the thrombi were removed using Randall's clamps. Flushing with 1:200 heparin solution was carried out. At this time, the bleeding from the lumbar veins was not serious and did not jeopardize the removal of the thrombi with good visibility. The vessels were closed with a running prolene suture. During the period of clamping, which lasted for 12 minutes, there was light arterial hypotension, controlled by the anesthesiologist. The clamps were removed in reverse order (Figure 1).

Figure 1 Hematoxylin-eosin staining showing vascular invasion of the malignant pheochromocytoma.

The patient became free of symptoms for six years, with normal catecholamine serum levels. After this period, a rise in arterial blood pressure level was found during a medical follow-up assessment. The norepinephrine serum level was found to be 3347 (normal 40 to 268 pg/ml) and urinary norepinephrine 741 (normal 65 to 400 mcg/24h). The epinephrine serum level was normal. The CT scan of the abdomen revealed a pre-aortic mass of 3 × 4 cm situated immediately below the renal artery (Figure 2). The existence of the mass was confirmed by magnetic resonance imaging (MRI), appearing with hypersignal in T2. The radioisotope study with meta-iodobenzyl-guanidine (MIBG) demonstrated considerable enhancement of the tumor.

Figure 2 CT scan of the abdomen showing a 3 × 4 cm pre-aortic mass.

The surgical removal of the mass described was undertaken by median laparotomy with retroperitoneal dissection. A frozen biopsy of the specimen showed free margins. The normal postoperative catecholamine levels confirmed the total removal of the tumor.

Alpha and beta-blockers (prazosin and propranolol, respectively) were used as preoperative treatment in both operations. The adrenergic blockage was begun 15 days before the surgery with gradual adjustment of dosage, reaching 6 mg of prazosin and 80 mg of propranolol per day. The pathological study of the specimen showed malign pheochromocytoma with free margins. The patient is well after a 7-year follow-up.

DISCUSSION

The invasion of the inferior vena cava has already been described in relation to many abdominal tumors. The retroperitoneal tumor most commonly associated with extension into this vessel is renal cell carcinoma12 but it rarely occurs in pheochromocytomas. The extension may occur by direct invasion of the vessel wall or by luminal progression within the vein. The direct invasion is more frequently observed in malignant neoplasia.17 The technique of choice employed by many authors for the removal of tumors that present a thrombus inside the infra or supra-hepatic vena cava without affecting the right atrium utilizes extra corporeal circulation with hypothermia and total cardiac arrest for their safe removal.12 However, in such cases, radical surgery is also practicable without the use of extra corporeal circulation,20 thus avoiding the morbidity related to this procedure as well as the increase in hospital costs, as demonstrated in our case.

Others prefer to use the piggyback style of mobilization of the liver to access the inferior vena cava, which is the technique employed for orthotopic liver transplantation.21 The extension of the tumor into the inferior vena cava with no invasion of the vessel wall does not necessarily mean malignancy,22 which occurs when there is direct invasion of the vessel wall.23 The presence of distant metastases is the unquestionable criterion for the classification of malignant pheochromocytoma.24 Although malignant pheochromocytomas tend to reappear or present metastases during long-term follow-up, surgical removal of these tumors is the best option for treatment,25 considering that the patients have a ten year survival rate with no evidence of disease.

The incidence of extra adrenal pheochromocytomas or multicentric tumors varies from 3.8 to 10%,26,27 the most common site being Zuckerkandl's organ. In these cases, where the concentration of norepinephrine is considerably greater than that of epinephrine, the existence of extra adrenal pheochromocytoma may be suspected, as the methylation occurs mainly in the adrenal gland. This was observed in the case presented. In rare cases, measurement of plasma catecholamine values in blood samples taken from different levels of the inferior vena cava may also be useful in the search for possible sites of metastases.26

At present, MRI is tending to become the method of choice for the assessment of thrombi in the large vessels, visualized mainly in T1 and T2 sequences.17 In the past, laparotomy was the approach of choice for pheochromocytomas because of the frequency of bilateral disease and the possibility of the existence of extra adrenal tumors misdiagnosed prior to surgery. Nevertheless, with the improvement in methods of localization such as CT scan, MRI and MIBG scintigraphy, the surgeon enjoys the possibility of choosing the best surgical approach beforehand.

The use of alpha and beta blocking agents preoperatively ensures a fully expanded vascular system and also minimizes intraoperative blood pressure fluctuation. Recently, the use of other drugs such as calcium channel blockers, instead of alpha and beta adrenergic antagonists has been demonstrated.28 However, due to the effectiveness and low costs of alpha and beta blocking agents, they are still being used as drugs of choice in our experience.

Antonio Marmo Lucon, MD, PhD. Associate Professor, Division of Urology, Department of Surgery, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Renato Falci Júnior, MD. Resident in Urology, Division of Urology, Department of Surgery, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

José Nery Praxedes, MD, PhD. Associate Professor, Department of Nephrology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Marcel Cerqueira Cesar Machado, MD, PhD. Associate Professor, Division of Gastroenterological Surgery, Department of Surgery, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Luis Balthazar Saldanha, MD, PhD. Associate Professor, Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Marcelo Marcondes Machado, MD, PhD. Full Professor and Head, Department of Nephrology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Sami Arap, MD, PhD. Full Professor and Head, Division of Urology, Department of Surgery, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Sources of funding: Not declared

Division of Urology, Hospital das Clínicas, Faculty of Medicine, Universidade de São Paulo, São Paulo, Brazil
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REFERENCES

1 Korobkin M Francis IR Kloos RT Dunnick NR The incidental adrenal mass Radiol Clin North Am 1996 34 5 1037 1054 8784395
2 Bravo EL Gifford RW Jr Current concepts – pheochromocytoma: diagnosis, localization and management N Engl J Med 1984 311 20 1298 1303 6149463
3 Young JD Jr Qureshi AS Connor TB Wiswell JG Problem lesion in adrenal surgery J Urol 1969 101 233 240 5765866
4 Rote AR Flint LD Ellis FH Jr Intracaval recurrence of pheochromocytoma extending into right atrium. Surgical management using extra corporeal circulation N Engl J Med 1977 296 1269 1271 859517
5 Costello P Clouse ME Kane RA Paris A Problems in the diagnosis of adrenal tumors Radiology 1977 125 335 341 910042
6 Scott HW Reynolds V Green N Page D Oates JA Robertson D Clinical experience with malignant pheochromocytoma Surg Gynecol Obstet 1982 154 801 818 7079921
7 Russinovich NAE Recio MG Tishler JM Zornes SL Luna RF Intracaval extension of pheochromocytoma: ultrasonographic demonstration Can Assoc Radiol J 1982 33 53 55
8 Hoffman JC Weiner SN Koenigsberg M Morehouse H Smith T Pheochromocytoma invasion of the inferior vena cava: sonographic evaluation Radiology 1983 149 793 795 6647857
9 Smith EJ McPherson GAD Lynn J Inferior vena cava involvement by a pheochromocytoma Br J Surg 1987 74 597 597 3620868
10 Dicke TE Henry ML Minton JP Intracaval extension of pheochromocytoma simulating pulmonary embolism J Surg Oncol 1987 34 160 164 3546948
11 Levine E de Vries P Wetzel LH MR imaging of inferior vena cava recurrence of extra-adrenal pheochromocytoma: a case report J Comput Assist Tomogr 1987 11 717 718 3597902
12 Novick AC Kaye MC Cosgrove DM Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena cava thrombi Ann Surg 1990 212 4 472 476 2222013
13 Dumm CW Snyder WH Ring WS Latson TW Pheochromocytoma with extension into the inferior vena cava: a case report Surgery 1992 111 4 472 474 1557694
14 Boneschi M Miani S Erba M Giuffrida GF Giordanengo F Malignant neoplasms invading into the inferior vena cava Minerv Cardioangiol 1995 43 3 91 95
15 Raghavan R Ince PG Walls TJ Gholkar A Dark JH Foster JB Malignant cerebrovascular thromboembolization by pheochromocytoma Clin Neuropathol 1995 14 2 69 71 7606899
16 Rotker J Oberpenning F Scheld HH Hertle L Knichwitz G Hammel D Pheochromocytomas with extension into central vascular structures Ann Thorac Surg 1996 61 1 222 224 8561564
17 Lau TN Goddard P Vaidya M Calloway M Bullimore J Involvement of the inferior vena cava by adrenal pheochromocytoma: MRI findings Br J Radiol 1997 70 303 305 9166057
18 Melicow MM One hundred cases of pheochromocytoma (107 tumors) at the Columbia Presbyterian Medical Center, 1926-1976 Cancer 1997 40 1987 2004
19 Arroja JM Gudinchet F Maeder P Fournier D Phéochromocytome multiple familial: démonstration échographique de multiples localisations surrénaliennes, coeliaques et vésicales chez un enfant Schweiz Rundsch Med Prax 1995 84 43 1231 1234
20 Hedican SP Marshall FF Adrenocortical carcinoma with intracaval extension J Urol 1997 158 6 2056 2061 9366311
21 Ciancio G Hawke C Soloway M The use of liver transplantation technique to aid in the surgical management of urological tumors J Urol 2000 164 665 672 10953122
22 Dunnick NR Dompman JL Geelhoed GW Intravenous extension of endocrine tumors A J R 1980 135 471 476
23 Meyers MA King MC Unusual radiological features of pheochromocytoma Clin Radiol 1969 20 52 56 5774091
24 Davis P Malignant pheochromocytoma with functioning metastases Lancet 1955 269 274 275 13243711
25 Mahoney EM Harrison JH Malignant pheochromocytoma: clinical course and treatment J Urol 1977 18 2 225 229
26 Delarue NC Morrow JD Kerr JH Colapinto RF Pheochromocytoma in the modern context Can J Surg 1978 21 5 387 394 31234
27 van Heerden JA Roland CF Carney JA Sheps SG Grant CS Long-term evaluation following resection of apparently benign pheochromocytoma(s)/ paraganglioma(s) World J Surg 1990 14 3 325 329 1973322
28 Ulchaker JC Goldfarb DA Bravo EL Novick AC Successful outcomes in pheochromocytoma surgery in the modern era J Urol 1999 161 3 764 767 10022680
