Pheochromocytomas of the vesical and paravesical region
We report our experience with four cases of vesical and paravesical pheochromocytomas treated in our hospital over the past 15 years.
Authors: Nitin Kapoor1,M.S Seshadri 1,Nihal Thomas1, Antony Devasia2
John Banerjee2, Ramani Manoj Kumar3,Simon Rajaratnam1
1. Department of Endocrinology; 2 Department of Urology; 3 Department of Pathology, Christian Medical College, Vellore, India
Corresponding Author: Dr Simon Rajaratnam, Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India. 632004. Email: [email protected] ; Phone: +91-416-2282528
Abstract
Purpose
Pheochromocytomas of the urinary bladder are extremely rare. They account for less than 0.06% of all the tumors arising from the urinary bladder. Even though 10% of pheochromocytomas occur at extra adrenal sites, barely 1% arise from the urinary bladder. Embryonic rests of chromaffin tissue within the sympathetic plexus in the bladder wall are the source of these tumors. Due to varied symptomatology and nonspecific physical findings, a high index of suspicion is required for accurate diagnosis. Therapeutic strategies are not well-defined owing to the rarity of these tumors.
Material and Methods
We report a series of four cases of vesical and para vesical pheochromocytoma treated in our hospital over the past 15 years. Here, the authors have described the clinical presentation, physical findings, laboratory investigations and treatment provided in all the 4 cases. We have also included radiological images and histopathology slides with input from both radiologists and pathologists. Surgical management and post-operative follow up are discussed, as are details of previous published data.
Results and Conclusion
Bladder pheochromocytomas are rare but unique tumors. We share our experience with four cases treated in our hospital.
Introduction
Pheochromocytomas of the urinary bladder are extremely rare. They account for less than 0.06% of all tumors arising from the urinary bladder. [1, 2] Even though 10% of pheochromocytomas occur in extra adrenal sites, barely 1% arise from the urinary bladder.[3] Embryonic rests of chromaffin tissue arising from the sympathetic plexus within the bladder wall are the source of these tumors .[4] Due to varied symptomatology and nonspecific physical findings, a high index of suspicion is required for accurate diagnosis. Therapeutic strategies are not well-defined owing to the rare occurrence of these tumors.
We report our experience with four cases of vesical and paravesical pheochromocytomas treated in our hospital over the past 15 years.
Case Report 1
A 28 year old woman presented in 1996 with a history of recurrent episodes of chest pain with profuse sweating and palpitation for 4 years, 5 these episodes usually occurred during micturition or soon after micturition. One month prior to admission she also had an episode of hematuria. Prior to the onset of her symptoms she went through two uneventful vaginal deliveries. Her family history was unremarkable.
On examination, her pulse rate was 90/min and blood pressure 140/90 mmHg. After micturition her pulse rate increased to120/min and blood pressure increased to 160/110 mmHg. Cardiovascular, respiratory system, abdominal and CNS examination were all normal. No bruits were heard over the abdomen. Fundus examination revealed grade 2 hypertensive changes.
Her full blood count and urea and electrolytes were normal. Urine microscopy was normal; there was no proteinuria or glycosuria. Twenty four hour urinary Vanillyl Mandelic Acid (VMA) levels were elevated at 8 mg and 11mg (normal <7 mg/24 hours). ECG revealed sinus tachycardia with no evidence of LVH. Chest X ray was normal. Ultrasound revealed an intravesical mass extending into the perivesical space. MIBG (Meta-Iodo-Benzyl-Guanidine) scan showed tracer uptake over the tumor.
After adequate control of blood pressure she underwent partial cystectomy. The post operative period was uneventful and all anti-hypertensive agents were successfully withdrawn. She has remained asymptomatic on follow up.
Case Report 2
A 50 year old man who was being treated for diabetes and hypertension presented in 1999, with a one year history of fatigue, weight loss, palpitations and breathlessness. Routine ultrasound examination revealed a paravesical mass. CT scan revealed a large 10 x 10 cm heterogeneous mass at the superior aspect of the prostate and base of the bladder, extending up to the symphysis pubis. He had no bowel or micturition related symptoms. He underwent laparotomy at his local hospital. Since the tumor could not be excised he was referred to us for further management. A biopsy was reported as showing a paraganglioma. MIBG scan showed uptake over the tumor. He underwent cysto-prostatectomy with Mainz II pouch diversion. The immediate post-operative period was uneventful, however he later developed sepsis and succumbed on the 10th postoperative day.
Case Report 3
A 28 year old woman, presented in 2010 with a history of intermittent severe headache for 15 years. Two years following the onset of these symptoms she had an episode of severe headache and loss of consciousness. She was hospitalized and was found to have sustained a right hemiparesis secondary to an intracerebral bleed. She gradually regained motor power on the affected side, but continued to experience frequent headaches.
One year before she started complaining of blurring of vision and was found to have severe hypertension. Her documented blood pressure readings were as high as 210/140 mmHg. She complained of severe headache, palpitations and sweating following micturition.
On examination her blood pressure was 150/110 mmHg. Following micturition her blood pressure rose to 190/130 mmHg. There were no bruits over her abdomen. She had grade 1 hypertensive changes in her fundi. The rest of the systemic examination was normal.
On investigation she had mild anemia. Her serum calcium, phosphorus, electrolytes and creatinine were normal. Urine examination showed no abnormality. Her chest X-ray, ECG and echocardiogram showed left ventricular hypertrophy. Her 24 hour urinary metanephrine level was 88 μg/1450 ml (normal < 350 μg/24 hour) and urinary
nor-metanephrine level was 1848 μg/1450 ml (normal <600 μg/24 hour).
CT angiogram revealed a 4.3 x 4 cm hypervascular mass in the inferolateral wall of the urinary bladder bulging into the lumen. Her MIBG scan however showed no uptake over the lesion.
After adequate control of blood pressure she proceeded to surgery. Cystoscopy revealed a normal external urethral meatus, normal urethra and ureteric orifices. The bladder mucosa appeared normal. At laparotomy, there was a 5 x 5 cm mass involving the anterior and left lateral wall of the bladder. At cystotomy, the mucosa appeared normal but the tumor could be felt extending up to the bladder neck, adjacent to the ureteric orifice. A partial cystectomy was performed and the tumor was excised with a margin beyond its palpable edge. The postoperative period was uneventful and her anti-hypertensive medication was discontinued. Histopathological examination revealed features of pheochromocytoma, with typical ‘zell-ballen’ arrangement of tumour cells, separated by a delicate network of capillary sized blood vessels. There was mild nuclear pleomorphism, but no evidence of malignancy. The tumour cells were positive for Chromogranin A, synaptophysin, and negative for cytokeratin (Fig 1 & 2).
Figure 1.
Figure 2.
At subsequent follow up her urinary nor- metanephrine level had normalized (180 µg/24 hours), she however needed to be restarted on antihypertensive medication. Follow up cystogram was normal.
Case Report 4
A 24 year old man presented in 2011 with intermittent painless hematuria for 12 years. There was no history of headache, blurred vision, palpitations or syncope. He was not on any medication. He had been evaluated elsewhere and found to have a bladder tumor for which he underwent 4 transurethral resections over a period of 9 years. An open resection was also attempted but surgery was abandoned as the patient developed extremely high intraoperative blood pressure.
The patient was evaluated at our centre and found to have elevated urinary nor-metanephrine levels (3019 µg/24 hours) and normal urinary metanephrine levels (141 µg/24 hours). His MIBG scan showed a functioning neuroendocrine tumor in the superolateral aspect of the bladder. CT scan revealed a well defined enhancing mass lesion arising from the right lateral wall of the urinary bladder.
Figure 3.
Cystoscopy under general anesthesia revealed a 3 x 3 cm extra mucosal mass arising from the right lateral bladder wall, above the right ureteric orifice. There was a 1X1cm ulcerated area at the center of the lesion. The left ureteric orifice and the rest of the bladder mucosa were found to be normal. We proceeded with excision of the mass with partial cystectomy. The mass was found to be adherent to the lateral pelvic wall probably due to previous attempts at excision. There was no fluctuation of blood pressure during surgery. Histopathology of the tumour came back as showing malignant pheochromocytoma arising from the bladder wall. On follow up his urinary metanephrine levels have normalized and he has remained asymptomatic.
Figure 4.
Figure 5.
Discussion
Pheochromocytoma of the urinary bladder is a rare tumor. Such tumors arise from the chromaffin tissues associated with sympathetic nerves located within the bladder wall. They are hormonally active and cause symptoms including palpitations, sweating, headache and hypertension (paroxysmal/sustained). These symptoms are usually precipitated by micturition.[6] A rise in blood pressure can be demonstrated immediately following micturition. The other precipitating factors include abdominal palpation, defecation and sexual intercourse. However, not all patients demonstrate these signs and symptoms due to receptor down regulation following prolonged catecholamine exposure. Signs and symptoms of urethral obstruction may also occur. [7] Painless hematuria occurs in 50-60% of patients. The diagnosis of this condition warrants a high index of clinical suspicion.
The most useful laboratory test is to determine blood and urinary catecholamine levels and measure their metabolic byproducts. Urinary VMA levels >9.0 mg/24 hours, nor epinephrine > 80 μg/24 hours and epinephrine > 20 μg/24 hours have been found in most patients. While CT/MR aid in the anatomical localization of these tumors, iodine-131– metaiodobenzylguanidine (MIBG) and indium-111 pentoctreotide scintigraphy serve as complementary functional diagnostic tools as they have 85-100% sensitivity in localizing these tumors.[8,9] One of our patients, (case 3) however had a negative MIBG scan. Positron emission tomography (PET) using 6 – [18F] fluorodopamine is a more recently developed tool for imaging these tumors.
As preoperative preparation patient require alpha adrenoreceptor blockers for at least 2 weeks, beta blockers are subsequently added to control heart rate. They also need adequate hydration to increase intravascular volume prior to surgery.
Most vesical pheochromocytomas are intramural as the sympathetic plexus is scattered between all the layers of the bladder wall. At cystoscopy these tumors may appear granulated and lobulated with or without ulceration.[2] Transurethral resection is not recommended as it will not remove the entire tumor. Open surgery is required to completely resect these tumors. [2,7,11] Laparoscopic tumor resection has also been attempted.[10]
As part of the intraoperative strategy, the use of cystoscopic examination may help delineate the exact location of these tumors and identify the depth of invasion and the involvement of the ureters. However, cystoscopic examination in case 3 was non-contributory probably due to the intramural nature of the tumor. In this case excision with a margin was guided by palpation. A thorough examination of surrounding structures and regional lymph nodes should be done as the malignant potential of these tumors is predicted not by histology but by clinical evaluation. In addition, these patients should also be monitored for post-operative complications such as stricture or obstruction at the urethral reimplantation site.
Overall, pheochromocytomas of the urinary bladder have a slightly better prognosis as compared to other extra adrenal pheochromocytomas. As these tumors are known for recurrence and metastases, these patients will require lifelong follow up. Though the diagnosis of pheochromocytoma is confirmed biochemically and the tumor located by using imaging techniques, biochemical evidence of excess catecholamine production usually antedates clinical symptoms, and therefore annual determination of urinary catecholamine / metabolites is recommended.[13,14] Prognosis will depend on the presence of familial endocrinopathy or the presence of metastases .[11]
In summary, due to varied symptomatology and nonspecific physical findings, a high index of suspicion is often required for accurate diagnosis and management of these patients.[15]
References
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3. Salanitri J, Smith P, Schlicht S. Multifocal malignant extra-adrenal paragangliomas of the Organ of Zuckerkandl and urinary bladder. Australas Radiol 2001; 45:229-32.
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9. Nakatani T, Hayama T, Uchida J, et al. Diagnostic localization of extra-adrenal pheochromocytoma: Comparison of (123)I-MIBG imaging and (131)I-MIBG imaging. Oncol Reports 2002; 9:1225-7.
10. Kozlowski PM, Mihm F, Winfield HN. Laparoscopic management of bladder pheochromocytoma. Urology 2001; 57:365.
11. Hwang JJ, Shoaf G, Uchio EM, et al. Laparoscopic management of extra-adrenal pheochromocytoma. J Urol 2004; 171:72-6.
12. Snavely MD, Mohan LC, O’Conor DT, Insel PA (1983) Selective down regulation of adrenergic receptor subtype in tissues from rats with pheochromocytoma. Endocrinology 113:354–361
13. Whalen RK, Althausen AF, Gilbert HD (1992) Extra-adrenal pheochromocytoma. J Urol 147:1–10
14. Ahmed S. Safwat, Nabil K. Bissada, Raouf M. Seyam, Saif Al Sobhi, Kamal A. Hanash. The clinical spectrum of pheochromocytoma: analysis of 115 patients. BJUI 2008; 101: 1561-1564
15. Safwat S. Ahmed; Bissada K. Nabil. Pheochromocytoma of the urinary bladder. Can J Urol 2007; 14: 3757 – 3760
Date added to bjui.org: 08/08/2012
DOI: 10.1002/BJUIw-2011-144-web
