Successful surgical treatment for life threatening metastatic thoracic and cervical pheochromocytoma
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《血管的通路杂志》
1 Department of Thoracic Surgery, Graduate school of medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670
2 Department of Basic Pathology, Graduate school of medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670
Abstract
A 53 year-old woman had been followed up since 1996 after receiving bilateral adrenalectomy for the treatment of bilateral adrenal pheochromocytoma in von Hippel-Lindau (VHL) disease. In March 2003, she suffered from cough, dizziness and faint, and was referred to our hospital. The radiographic findings exhibited the presence of hypervascular tumors in the left hilum, left apex of the lung and the left neck. Tumor progression was suspected to occlude the left main pulmonary artery and hormonal assays showed elevated levels of the plasma norepinephrine, which may cause fatal complications. Percutaneus needle biopsy of the left cervical tumor revealed metastatic pheochromocytoma. After embolization of the main feeding artery, surgical resection of the tumor resulted in control of excess catecholamine release and symptoms.
Key Words: Surgery; thoracic pheochromocytoma; embolization; von Hippel-Lindau disease
1. Case report
A 53 year-old woman had been followed up at our hospital since 1996 after receiving bilateral adrenalectomy for the treatment of bilateral adrenal pheochromocytoma. She was diagnosed as von Hippel-Lindau (VHL) disease in 1999, since she not only had pheochromocytoma, but also had hemangioma of the cerebellum, pancreatic cyst, and VHL disease gene in her daughter. In March 2003, she suffered from cough, dizziness and faint and was referred to our hospital. A chest X-ray film on admission showed prominence of the aortic knob. Chest CT scan, MRI scan of the chest, and positron emission tomography with fluorodeoxyglucose (FDG-PET) exhibited the presence of hypervascular tumors in the left hilum, left apex of the lung and the left neck (Fig. 1). 131I-meta-iodobenzyl guanidine (MIBG) scanning did not exhibit a high accumulation of tracer in these tumors, although it showed positive accumulation when bilateral adrenalectomy was performed in 1996. The tumor in the left hilum located at the AP window surrounded the left main pulmonary artery. Endocrinological examination revealed the following: plasma epinephrine, 5 pg/ml (normal: <100 pg/ml) and plasma norepinephrine, 9128 pg/ml (100-450 pg/ml). The serum CEA, proGRP and CYFRA were within normal limits. The serum NSE was 41.88 ng/ml (<10 ng/ml). On the basis of the radiographic findings, the results of endocrinology and tumor marker, pre-surgical diagnosis suggested recurrent extra-adrenal pheochromocytoma, or hormone producing lung cancer. Trans bronchial needle aspiration of the tumor was performed, but could not obtain a firm diagnosis. Therefore percutaneus needle biopsy of the left cervical tumor was performed and revealed metastatic pheochromocytoma.
Embolization of the main feeding artery, left intra-thoracic artery, detected by 3D-CT was performed and resulted in a decrease of norepinephrine value. In order to control hormonal symptoms and tumor progression, surgery was performed through median sternotomy. Pump-oxygenator and absorption column for catecholamine were prepared each for massive bleeding from the hypervascular tumors and for hemodynamic fluctuations. After the resection of the small left cervical tumor, left pneumonectomy was performed in order to stabilize the hormonal balance during surgery with manipulation of the tumor. The tumor which was located at the AP window did not invade the ascending aorta and trunk of pulmonary artery, however involved the left main pulmonary artery and A6. The surgery was successfully performed without massive bleeding or hemodynamic fluctuations, so pump-oxygenator and absorption column for catecholamine was not used.
A high-power view of the resected specimen showed ovoid tumor cells with an abundant granular cytoplasm. These cells were divided into nests with vascular stroma, which ware similar to the original specimen. Extensive hemorrhage and necrosis were also shown. Immunohistochemical staining for chromogranin, which is a marker for neuroendocrine tumors, was strongly positive(Fig. 2). The pathological diagnosis of the three tumors was metastatic pheochromocytoma.
The plasma norepinephrine value (640 pg/ml) dramatically lowered after the surgery and hormonal symptoms were well controlled. Post-surgical course was good except for deep venous thrombosis of her legs at 13 days post-operation, which required anticoagulant therapy.
2. Discussion
The incidence of pheochromocytoma ranges from 0.3 to 0.95% of all neuroendocrine tumors, which arise from chromaffin tissues of the sympathetic nervous system [1]. About 90% of pheochromocytomas are located below the diaphragm, with 85 to 95% occurring in the adrenal medulla. Intrathoracic lesions occur in 10% of the patients. In addition, head and neck lesions occur only in 3% [2]. A case with both metastatic thoracic and cervical pheochromocytoma is very rare.
The definitive cure is surgery for well-localized tumors along with concurrent medical management of catecholamine excess, hypertension, hypovolemia and hypoglysemia. When recurrences or metastases are demonstrated, surgical removal or debulking is the treatment of choice to relieve symptoms and control hypertension. Except for surgical therapy, no other forms of therapy are curative. The roles of chemotherapy, external beam radiation and 131I-MIBG therapy are still under investigation [2]. In this case, although the tumors were metastatic, complete resection of the tumors was the only way to control hormonal symptoms and tumor progression. Surgery was successfully performed with preoperative antihypertensive medications and intra-arterial embolization.
There is a high necessity for frequent and life-long follow-up in metastatic pheochromocytoma with VHL disease. Current guidelines recommend yearly abdominal CT for pheochromocytoma and renal cell carcinoma (from age 20), yearly abdominal ultrasound (age 11-20), enhanced MRI image of brain and spinal chord for hemangioblastoma every other year (from age 11), yearly ophthalmoscopy for retinal angiomas (from infancy) and urinary catecholamines (from age 2) [3]. This case was falsely negative for the 131I-MIBG scanning which had been positive with the original adrenal pheochromocytoma, but positive for FDG-PET. After a 6-month follow up using FDG-PET, our patient is healthy and shows no signs of recurrence.
References
Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc 1983;58:802–804.
Sunder S, Asok D, Joel LS, Aleejandro AC, Mehta AC. Thoracic involvement with pheochromocytoma (review). Chest 1999;115:511–521.
Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology 1995;194:629–642.(Tomoyasu Yashiro, MD, Kaz)
2 Department of Basic Pathology, Graduate school of medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670
Abstract
A 53 year-old woman had been followed up since 1996 after receiving bilateral adrenalectomy for the treatment of bilateral adrenal pheochromocytoma in von Hippel-Lindau (VHL) disease. In March 2003, she suffered from cough, dizziness and faint, and was referred to our hospital. The radiographic findings exhibited the presence of hypervascular tumors in the left hilum, left apex of the lung and the left neck. Tumor progression was suspected to occlude the left main pulmonary artery and hormonal assays showed elevated levels of the plasma norepinephrine, which may cause fatal complications. Percutaneus needle biopsy of the left cervical tumor revealed metastatic pheochromocytoma. After embolization of the main feeding artery, surgical resection of the tumor resulted in control of excess catecholamine release and symptoms.
Key Words: Surgery; thoracic pheochromocytoma; embolization; von Hippel-Lindau disease
1. Case report
A 53 year-old woman had been followed up at our hospital since 1996 after receiving bilateral adrenalectomy for the treatment of bilateral adrenal pheochromocytoma. She was diagnosed as von Hippel-Lindau (VHL) disease in 1999, since she not only had pheochromocytoma, but also had hemangioma of the cerebellum, pancreatic cyst, and VHL disease gene in her daughter. In March 2003, she suffered from cough, dizziness and faint and was referred to our hospital. A chest X-ray film on admission showed prominence of the aortic knob. Chest CT scan, MRI scan of the chest, and positron emission tomography with fluorodeoxyglucose (FDG-PET) exhibited the presence of hypervascular tumors in the left hilum, left apex of the lung and the left neck (Fig. 1). 131I-meta-iodobenzyl guanidine (MIBG) scanning did not exhibit a high accumulation of tracer in these tumors, although it showed positive accumulation when bilateral adrenalectomy was performed in 1996. The tumor in the left hilum located at the AP window surrounded the left main pulmonary artery. Endocrinological examination revealed the following: plasma epinephrine, 5 pg/ml (normal: <100 pg/ml) and plasma norepinephrine, 9128 pg/ml (100-450 pg/ml). The serum CEA, proGRP and CYFRA were within normal limits. The serum NSE was 41.88 ng/ml (<10 ng/ml). On the basis of the radiographic findings, the results of endocrinology and tumor marker, pre-surgical diagnosis suggested recurrent extra-adrenal pheochromocytoma, or hormone producing lung cancer. Trans bronchial needle aspiration of the tumor was performed, but could not obtain a firm diagnosis. Therefore percutaneus needle biopsy of the left cervical tumor was performed and revealed metastatic pheochromocytoma.
Embolization of the main feeding artery, left intra-thoracic artery, detected by 3D-CT was performed and resulted in a decrease of norepinephrine value. In order to control hormonal symptoms and tumor progression, surgery was performed through median sternotomy. Pump-oxygenator and absorption column for catecholamine were prepared each for massive bleeding from the hypervascular tumors and for hemodynamic fluctuations. After the resection of the small left cervical tumor, left pneumonectomy was performed in order to stabilize the hormonal balance during surgery with manipulation of the tumor. The tumor which was located at the AP window did not invade the ascending aorta and trunk of pulmonary artery, however involved the left main pulmonary artery and A6. The surgery was successfully performed without massive bleeding or hemodynamic fluctuations, so pump-oxygenator and absorption column for catecholamine was not used.
A high-power view of the resected specimen showed ovoid tumor cells with an abundant granular cytoplasm. These cells were divided into nests with vascular stroma, which ware similar to the original specimen. Extensive hemorrhage and necrosis were also shown. Immunohistochemical staining for chromogranin, which is a marker for neuroendocrine tumors, was strongly positive(Fig. 2). The pathological diagnosis of the three tumors was metastatic pheochromocytoma.
The plasma norepinephrine value (640 pg/ml) dramatically lowered after the surgery and hormonal symptoms were well controlled. Post-surgical course was good except for deep venous thrombosis of her legs at 13 days post-operation, which required anticoagulant therapy.
2. Discussion
The incidence of pheochromocytoma ranges from 0.3 to 0.95% of all neuroendocrine tumors, which arise from chromaffin tissues of the sympathetic nervous system [1]. About 90% of pheochromocytomas are located below the diaphragm, with 85 to 95% occurring in the adrenal medulla. Intrathoracic lesions occur in 10% of the patients. In addition, head and neck lesions occur only in 3% [2]. A case with both metastatic thoracic and cervical pheochromocytoma is very rare.
The definitive cure is surgery for well-localized tumors along with concurrent medical management of catecholamine excess, hypertension, hypovolemia and hypoglysemia. When recurrences or metastases are demonstrated, surgical removal or debulking is the treatment of choice to relieve symptoms and control hypertension. Except for surgical therapy, no other forms of therapy are curative. The roles of chemotherapy, external beam radiation and 131I-MIBG therapy are still under investigation [2]. In this case, although the tumors were metastatic, complete resection of the tumors was the only way to control hormonal symptoms and tumor progression. Surgery was successfully performed with preoperative antihypertensive medications and intra-arterial embolization.
There is a high necessity for frequent and life-long follow-up in metastatic pheochromocytoma with VHL disease. Current guidelines recommend yearly abdominal CT for pheochromocytoma and renal cell carcinoma (from age 20), yearly abdominal ultrasound (age 11-20), enhanced MRI image of brain and spinal chord for hemangioblastoma every other year (from age 11), yearly ophthalmoscopy for retinal angiomas (from infancy) and urinary catecholamines (from age 2) [3]. This case was falsely negative for the 131I-MIBG scanning which had been positive with the original adrenal pheochromocytoma, but positive for FDG-PET. After a 6-month follow up using FDG-PET, our patient is healthy and shows no signs of recurrence.
References
Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc 1983;58:802–804.
Sunder S, Asok D, Joel LS, Aleejandro AC, Mehta AC. Thoracic involvement with pheochromocytoma (review). Chest 1999;115:511–521.
Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology 1995;194:629–642.(Tomoyasu Yashiro, MD, Kaz)