Asian J Oral Maxillofac Surg. 2008;20:167-170.
Malignant Pheochromocytoma with Mandibular Metastasis Gosei Ueda,1,2 Hajime Sunakawa,2 Akira Arasaki,2 Keiichi Arakaki,2 Toshiyuki Nakasone,2 Tsutomu Higa2 1 Department of Oral and Maxillofacial Surgery, Okinawa Prefectural Miyako Hospital, and 2Department of Oral and Maxillofacial Functional Rehabilitation, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
Abstract Malignant pheochromocytoma of the mandible is an extremely uncommon tumour. This report describes a 59-year-old woman with pheochromocytoma metastatic to the mandible. The patient was referred with a painless mandibular swelling on the right side. She had undergone dual tumour ablation for a pheochromocytoma of the adrenal medulla 7 years and 6 months previously, and for a pheochromocytoma metastatic lesion on the pelvis 2 years and 8 months previously. Radiographic examinations revealed a well-circumscribed radiolucent lesion of the mandibular ramus. A definitive diagnosis of malignant pheochromocytoma was made following a partial mandibulectomy. The patient died of disseminated intravascular coagulation and multiple bone metastases of pheochromocytoma about 10 years after the initial diagnosis of disease. Key words: Mandible, Neoplasm metastasis, Pheochromocytoma
Introduction Pheochromocytoma is a catecholamine-producing uncommon tumour, which originates in enterochromaffin cells. Its occurrence peaks between the ages of 40 and 50 years and no gender predilection has been observed. Clinically, catecholamine produced by the tumour causes persistent or intermittent hypertension. The blood pressure increases rapidly in circumstances of stress, exercise, postural change, and surgery, with possible sudden death due to pulmonary oedema, congestive heart failure, cardiac infarction, or cerebral haemorrhage. However, many patients show a dramatic improvement in blood pressure levels after removal of the tumour.1 Malignant cases apparently account for 5 to 10% of these tumours. However, the only indicator of malignancy is metastasis. Although pheochromocytoma can metastasise to the bone, kidney or lung, only 2 such cases have been reported so far.2,3 This report is of a patient with malignant pheochromocytoma with mandibular metastasis.
Case Report A 59-year-old Japanese woman presented with a painless swelling in the right mandible. In November 1998, she consulted a hospital in Okinawa. An extensive diffuse radioCorrespondence: Gosei Ueda, DDS, PhD, Department of Oral and Maxillofacial Surgery, Okinawa Prefectural Miyako Hospital, 807 Higashinakasone, Hirara Miyakojima City, Okinawa 906-0007, Japan. Tel: (81 980) 723 151; Fax: (81 980) 743 105; E-mail: [email protected]
© 2008 Asian Association of Oral and Maxillofacial Surgeons.
lucent lesion in the right mandibular ramus was observed. As the tumour was suspected of being malignant, she was referred to the Department of Oral and Maxillofacial Functional Rehabilitation, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan, for detailed examination and treatment. Past medical history revealed that the patient had been diagnosed with hypertension in the 1980s. In March 1991, a movement disorder of the left lower extremity and discomfort in the left hand of unknown cause were noted, and she visited a general hospital for examination. In April 1991, the patient started treatment for hypertension at a city hospital, and an adrenal gland tumour was observed on abdominal ultrasonography. In July 1991, the adrenal gland was extirpated at the same hospital and a histopathological diagnosis of pheochromocytoma was made. The systolic blood pressure (200 mm Hg) at the beginning of treatment decreased to 130 mm Hg postoperatively. In 1996, the patient developed back pain and underwent a tumourectomy based on the diagnosis of a pelvic tumour at the same hospital. A subsequent pathological diagnosis of metastatic pheochromocytoma was made. She was taking oral amlodipine besilate since May 1998. Detailed family history showed that both parents had received treatment for hypertension. The patient’s father died from a subarachnoid haemorrhage at age 80 years, while her mother died of old age at 90 years. Three brothers and 6 sisters had no relevant history. Her general physical examination was within normal limits (height, 149 cm; 167
Pheochromocytoma with Mandibular Metastasis
Figure 1. Facial findings at initial presentation. A diffuse swelling is seen in the right mandible.
weight, 53 kg; body temperature, 35.7°C; pulse, 80/minute; pulse rhythm, regular; complexion, healthy; nutrition, good) except for hypertension (blood pressure, 156/90 mm Hg). At initial examination, her face was asymmetrical, with a diffuse swelling, 60 t 43 mm in size, in the right mandible. However, the skin covering the swelling was healthy in colour (Figure 1). An elastic soft movable lymph node (major axis, 8 mm) was felt under both mandibles. No nerve symptoms in the inferior alveolar innervation zone were observed. Intraoral findings revealed that teeth 17, 16, 25-27, 34-37, 44-47 were deficient, where partial dentures had been attached. Although a diffuse bone-like hard bulge was observed in the right anterior border of the mandibular ramus, the covering mucous membrane had a healthy colour and smooth surface, and was movable with no tenderness. The width of the opening was 36 mm, and mandibular deviation to the right and pain in the right condylar process were observed at the opening. Panoramic X-ray showed radiolucency with an indistinct border, which spread from the right ramus of the mandible to the coronoid and condylar processes (Figure 2). Magnetic resonance imaging (MRI) showed a high-signal clearbordered mass (major axis, 40 mm) on T2-weighted images, displacing the glandula parotidea and internal pterygoid muscle (Figure 3). In addition, a tumour mass (22 t 18 t
Figure 2. Panoramic radiography showing vague borders (arrows), extending to the coronoid and condylar processes in the right mandibular ramus. 168
Figure 3. T2-weighted frontal magnetic resonance image shows a hyperintense mass, measuring 40 mm along the major axis, with clear borders.
12 mm in size) extending from the lamellar bone in the left parietal bone and a mass (major axis, 50 mm) in the retroperitoneum were suspected of being a recurrence of the primary tumour. No abnormal images were observed in either lung field. Laboratory biochemical analyses showed slightly elevated values (glutamic oxaloacetic transaminase, 53 IU/L; glutamic pyruvic transaminase, 58 IU/L). A moderate ST reduction (>0.05 mV) was observed on electrocardiography. General blood and urine analyses gave normal results. Endocrinological examination of the adrenal gland revealed elevated parameters in the plasma (noradrenaline, 9588 pg/mL; dopamine, 3234 pg/mL) and urine (catecholamine, 3683.3 Mg/day; noradrenaline, 3675.6 Mg/day; dopamine, 5080.4 Mg/day). The clinical diagnosis was a recurrence of the adrenal gland tumour, with adrenal gland tumour metastasis to the mandibular and skull bones. As the tumour spanned 3 regions, treatment was administered at the Departments of Urology, Neurosurgery, and Oral and Maxillofacial Surgery. Total resection of the mandibular tumour was possible and, as the skull metastasis showed no infiltration into the brain parenchyma, special postoperative management of the resection was not thought necessary. Retreatment of the primary tumour after surgical removal of the metastatic tumour by means of collaborative surgery between the Departments of Neurosurgery and Oral and Maxillofacial Surgery was planned. High blood pressure, thought to be the result of increased catecholamine production, led to some difficulty in perioperative management. A segmental mandibulectomy and mandibular reconstruction with a metal plate were performed under propofol/ketamine/ fentanyl general anaesthesia on 18 December 1998, with postoperative intensive care unit management planned. The surgery was performed using both intra- and extraoral approaches. A skin incision was made from the lower lip/mental midline along the lower border of the mandible Asian J Oral Maxillofac Surg. Vol 20, No 3, 2008
Ueda, Sunakawa, Arasaki, et al
Figure 4. Soft radiograph of the sectional specimen showing significant bone resorption to have spread to the mandibular ramus and the coronoid and condylar processes.
and by mucous membrane incision to the anterior border of the mandibular ramus. The buccolabial periostea was separated, the right buccal mandibular bone was exposed, and the glandula parotidea and masseter muscle were separated to clearly show the region around the condylar process. The mandible was separated at the right mandibular molar region, the inside of the mandible was included in the tissue to be removed with the internal pterygoid muscle as an indicator, the malar bone and malar bone/temporal suture were exposed, the temporal muscle was cut off from the coronoid process, the tumour (inclusive of the condylar process) was removed, and soft radiography was performed (Figure 4). Reconstruction of the mandible and condylar process was done using a metal plate (Figure 5) and the incision was closed to complete the surgery. Bleeding during the surgery, which lasted 3 hours 30 minutes, was 1000 mL. Blood pressure (190/90 mm Hg) increased temporarily during the surgery, but was successfully managed with nicardipine hydrochloride and diltiazem hydrochloride. No paroxysmal blood pressure increase was observed postoperation, with the blood pressure remaining stable at 100/50 mm Hg when the patient was moved to the general ward 3 days after the surgery. The extirpated tumour was solid, yellowish, and encapsulated. Pathological examination of the specimen showed histology similar to the normal adrenal medulla, with a large circular eosinophilic nucleus and cytoplasm with vague borders. Although no mitosis was observed, there was an increase in the number of interstitial blood capillaries (Figure 6). The pathological diagnosis was malignant pheochromocytoma. Although postoperative examination of the adrenal endocrinological function showed high levels in the plasma (noradrenaline, 1761 pg/mL; dopamine, 1659 pg/mL) and urine (catecholamine, 355.7 Ng/day; noradrenaline, 348.5 Ng/day; dopamine, 3468.5 Ng/day), a significant reduction was observed in these parameters when compared with the preoperative levels. Asian J Oral Maxillofac Surg. Vol 20, No 3, 2008
Figure 5. Postoperative facial posteroanterior radiograph. Reconstruction of the mandible and condylar process was done using a metal plate.
The patient was transferred to the Department of Urology of a prefectural hospital 25 days after surgery. Following the transfer, a tumour embolism was observed in the inferior vena cava on MRI and palliative radiological treatment was conducted, resulting in a significant decrease of the size of the tumour recurrence. Administration of the hypotensive drug was stopped. An MRI done in March 1999 revealed multiple bone metastases, including in the left parietal bone. The patient died of multiple organ failure on 28 March 2001.
Discussion Pheochromocytoma is a tumour that occurs in the adrenal medulla. A tumour that occurs in the sympathetic paraganglion, such as the abdominal aorta, mediastinum or bladder, is called a paraganglionic cell tumour.1 However, because both tumours have the same cell form and endocrine function and their treatments are also the same, the latter is clinically called extra-adrenal pheochromocytoma, and both tumours are managed as for a broad pheochromocytoma in many cases.4,5 This tumour is called the ‘10% disease’, accounting for approximately 10% of extra-adrenal occurrence, twin-adrenal occurrence, and familial and malignant cases.4 The condition has clinical features of hypertension, hyperglycaemia, hypermetabolism, headache, and hyperhidrosis — symptoms known as the ‘5Hs’. However, the clinical symptoms and laboratory values are diverse, depending on the overproduction of catecholamine, which is often difficult to diagnose.5 Yanagi et al, who described a patient with mandibular metastasis of malignant pheochromocytoma, could not determine the findings to diagnose the tumour despite detailed imaging 169
Pheochromocytoma with Mandibular Metastasis
Figure 6. Histopathological examination. (a) Low magnification reveals histology similar to the normal adrenal medulla, with a solid tumour and growth of a number of interstitial capillaries (haematoxylin and eosin; original magnification, × 40). (b) High magnification shows a large circular eosinophilic nucleus, with a solid growth of tumour cells. The cytoplasm has slightly vague borders (haematoxylin and eosin; original magnification, × 400).
investigations, and reported that they obtained a diagnosis of non-functioning malignant pheochromocytoma by an explorative incision instead.3 Keiser established the following 7 items for diagnosis:5 (i) the 3 symptoms of headache, hyperhidrosis, and palpitation with or without hypertension; (ii) family history of pheochromocytoma; (iii) symptoms of multiple endocrine tumour; (iv) tumour mass in the adrenal gland, often as an accidental finding; (v) hypertension in association with catecholamine levels at the upper limits of normal range; (vi) hypertension for which standard treatment is ineffective; and (vii) a history of hypertension, tachysystole, and arrhythmia after anaesthesia, surgical management, and use of oral medicine. Appropriate patients should be measured for blood concentration of the meta derivative of catecholamine. The present patient had a history of malignant pheochromocytoma, which required extirpation of the right adrenal gland 7 years and 6 months previously, resection of a pelvic tumour 2 years and 8 months previously, and an abnormally high level of noradrenaline in the blood and urine, which made diagnosis of the case easy. Pheochromocytoma tends to improve dramatically after tumour extirpation, therefore extirpation is considered to be a priority for treatment. The treatment for malignant pheochromocytoma is similar, and extirpation is considered to be the only radical treatment. Perioperative management requires sufficient control of the blood pressure and includes transfusions and drug administration. In this patient, after making a diagnosis and scheduling surgical resection in consultation with the Departments of Neurosurgery, Radiology, Internal Medicine, and Urology — which had treated the primary tumour — collaborative perioperative management was carried out by physicians and the Department of Anaesthesia. In an earlier report of pheochromocytoma with mandibular metastasis, Fields et al reported perioperative bleeding of 1800 mL despite bronchotomy and hypotensive anaesthesia.2 170
In addition, repeat surgery had to be conducted on the night after surgery due to postoperative bleeding, which apparently made the resection of the tumour difficult.2 Much care should be taken during such resectional surgery to avoid any paroxysmal increase in blood pressure due to contact with the tumour. The systolic blood pressure in the present patient remained between 130 and 140 mm Hg during surgery, with a paroxysmal increase (190 mm Hg) being observed twice. However, systolic blood pressure remained between 110 and 120 mm Hg after mandibular resection. Treatment with cyclophosphamide, vincristine, and dacarbazine or large amounts of radiation with 131I-metaiodobenzylguanidine5,6 are performed for unresectable multiple metastases. However, the reported 5-year probability of survival is only 43%5 for the regimen as, even though production of catecholamine is inhibited and an improvement of clinical symptoms is expected, it is ineffective against tumour growth.4 This patient died 10 years after the first surgery.
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Yanagi Y, Asaumi J, Hisatomi M, Konouchi H, Wakasa T, Kishi K. Mandibular metastasis presenting as the initial manifestation of malignant pheochromocytoma. Eur J Radiol. 2002;44:5-9.
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Keiser HL. Pheochromocytoma and related tumors. In: DeGroot LJ, Jameson JL, editors. Endocrinology. Vol 3. 4th ed. Philadelphia: WB Saunders Co.; 2001.
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Asian J Oral Maxillofac Surg. Vol 20, No 3, 2008