182 Lebanese Medical Journal 2012 • Volume 60 (3)

CCAASS CCLLIINNIIQQUUEE// CCAASSEE RREEPPOORRTTBLADDER PARAGANGLIOMAA Case Reporthttp://www.lebanesemedicaljournal.org/articles/60-3/case5.pdf

Fouad EL KHOURY, Ibrahim JOUR, Bassem MALAEB, George ASSAF*

INTRODUCTION

Paragangliomas or extra-adrenal pheochromocytomasarise from sympathetic paraganglias and account for lessthan 0.05% of bladder tumors. Patients present usuallywith hematuria and micturition attacks characterized byhypertension episodes during micturition with systemicsymptoms of headache, blurred vision and palpitation dueto elevated plasma catecholamines [1, 17]. We present a case of bladder paraganglioma that was treated withpartial cystectomy.

CASE REPORT

A 32-year-old male patient presents with nine months his-tory of dyspnea, headache, and palpitations directly fol-lowing micturition. He does not report obstructive or irri-tative lower urinary tract symptoms. Medical history ispositive for controlled dyslipidemia. Vital signs assess-ment shows a blood pressure of 130/80 mmHg with heartrate of 75 beats per minute (bpm). Physical exam is unre-markable. He has no history of dyspnea upon exertion orat rest. He also does not report orthopnea or paroxysmalnocturnal dyspnea. Family history is not indicative of anyrelated condition.

Patient is examined after voiding and is found to havean elevated blood pressure of 170/100 mmHg along withtachycardia (100 bpm). Urinalysis shows microscopichematuria. Pelvic ultrasound reveals a left bladder wallpolyp measuring 35 x 23 mm observed on cystoscopy to be a submucosal pulsating mass around 3 cm in size(Figure 1a).

Computerized tomography of the chest, abdomen andpelvis confirms the presence of a 3 cm well circumscribedhomogenously enhancing soft tissue tumor arising fromthe left lateral wall with a convex outer border possiblyinvolving the muscularis layer but with preservation of the

El Khoury F, Jour I, Malaeb B, Assaf G. Bladder paragan-glioma: A case report. J Med Liban 2012 ; 60 (3) : 182-184.

El Khoury F, Jour I, Malaeb B, Assaf G. Paragangliome de lavessie : A propos d’un cas. J Med Liban 2012 ; 60 (3) : 182-184.

*From Urology Department, Saint George Hospital UniversityMedical Center, University of Balamand, Beirut, Lebanon.

Correspondence: George Assaf, MD. Department of Surgery.Saint George Hospital University Medical Center. Achrafieh.P.O. Box 166378. Beirut 1100 2807. Lebanon.

e-mail: assaf@wise.net.lbTel.: +961 3 29 29 15

ABSTRACT : This is a report of a 32-year-old manwho presented with dyspnea upon micturition. He wasfound to have hematuria. Pelvic ultrasound and CTscan of the abdomen and pelvis revealed a left bladderwall polyp confirmed by cystoscopy to be a submuco-sal pulsating mass. Plasma free metanephrines wereelevated in favor of a bladder paraganlioma while uri-nary metanephrines, catecholamines and MIBG scanwere normal. Patient was managed by partial cystec-tomy with disappearance of symptoms thereafter.Pathology showed a completely excised paraganglio-ma. The assessment, diagnosis and treatment are illus-trated.

RÉSUMÉ : Nous rapportons le cas d’un homme âgé de 32 ans présentant une dyspnée post mictionnelle.L’analyse des urines révèle une hématurie. Une écho-graphie pelvienne et un CT scan abdomino-pelvienrévèlent la présence d’un polype vésical gauche confir-mé par une cystoscopie qui montre une masse sous-muqueuse pulsatile. Le dosage des métanéphrines plas-matiques libres confirme une élévation en faveur d’unparagangliome vésical. Par contre, le dosage des méta-néphrines et des catécholamines urinaires montre unevaleur normale. Une scintigraphie à la méta-iodoben-zylguanidine (MIBG) est également normale. Le pa-tient subit une cystectomie partielle avec disparition deses symptômes. La pathologie montre une excisioncomplète d’un paragangliome. L’évaluation, le diag-nostic et le traitement seront discutés.

FIGURE 1a. Endoscopic view of the submucosal mass.

F. EL KHOURY et al. – Bladder paraganglioma, pheochromocytoma Lebanese Medical Journal 2012 • Volume 60 (3) 183

perivesical fat and with no lymphadenopathies or distantmetastatic disease (Figure 1b).

Biochemical assessment reveals elevated plasma freenormetanephrine (1.90 nmol/l; N : < 0.93), 348 ng/l (N < 170). However this value was not obtained directlypost micturition. 24 h urine catecholamines and meta-nephrines were within normal limits.

Iode 131-MIBG (methyl-iodobenzylguanidine) scin-tigraphy shows normal signal with no focal accentuationrelative to the urinary content. Patient’s clinical symptomsalong with the presence of a bladder polyp and elevatedplasma metanephrines suggest the presence of secretingbladder paraganglioma thus partial cystectomy is planned.Patient is prepared for surgical intervention by being puton an α-adrenergic blocker (doxasocin 1 mg, 2 tabs twicedaily) along with vigorous intravenous (IV) hydrationbefore surgery. Intra-operatively, care is taken to preventhypertensive crisis and intravenous nitroglycerin is pre-

pared. Partial cystectomy is performed under spinal anes-thesia with meticulous technique and care is taken not tomanipulate the mass and to leave an excision margin ofaround 0.5-1 cm. There is no recorded intra-operativeincrease in blood pressure or heart rate and surgery isuneventful. Besides severe bladder spasms, the patient hasa smooth postoperative recovery. Macroscopic descriptionof the specimen shows an encapsulated, well demarcated,beige brown soft nodule. Microscopically, completelyexcised paraganglioma is identified with a minor gan-glioneuroma component. Immunostain shows strong pos-itivity for synaptophysin and chromogranin in favor of aparaganglioma. On follow-up patient reports disappear-ance of his presenting symptoms.

DISCUSSION

Paragangliomas, or extra-adrenal pheochromocytomas,are tumors that arise from sympathetic paraganglia in rarelocations such as the thorax, bladder, or brain. Primaryparaganglioma of the bladder, arising from the submuco-sal paraganglionic cells, makes up less than 0.05% of allbladder neoplasms and less than 1% of all pheochromo-cytomas with 13 to 15% being malignant recognized by their clinical behavior with their capacity to metasta-size [1-3].

They occur in people of all races but less frequently inAfrican-Americans. Incidence peaks in the 3rd to 4th

decade with slight female predilection [3-4]. In children, the rate of malignancy is lower accounting

for up to 2% of cases [4]. The usual location of these tumors is at the dome of the

bladder or near the trigone. Half of the patients presentwith hematuria [3]. Similar to adrenal pheochromocytoma,they secrete catecholamines resulting into paroxysms ofhypertension, headache or syncope upon bladder filling or micturition in two-thirds of patients. The symptoms aremostly pronounced during urination resulting into mic-turition attacks especially if straining is needed duringbladder voiding [5]. Deep palpation over the pelvic area or bimanual exam may reproduce the above mentionedsymptoms [6].

These tumors can be sporadic or familial, inherited as part of multiple endocrine neoplasia type 2A or type2B, neurofibromatosis type 1 and von Hippel-Lindaudisease [7].

Imaging studies are necessary in determining tumorlocations and to rule out any presence of multifocallesions or metastases. On ultrasound, bladder pheochro-mocytomas appear as a well demarcated mass in the blad-der wall. If purely solid, they appear homogenous; how-ever, they may contain foci of hemorrhage and necrosisthus giving them a cystic appearance. CT scan with IVcontrast has a higher sensitivity, 94% in adrenal and 82%in extra-adrenal pheochromocytomas, in delineating therelationship between the mass and the bladder mucosa,muscularis and perivesical tissue [3, 8]. MRI is more sen-sitive than both ultrasound and CT scan. Those lesions,

CT scan revealing a well circumscribed mass in the bladder wall.

FIGURE 1b

184 Lebanese Medical Journal 2012 • Volume 60 (3) F. EL KHOURY et al. – Bladder paraganglioma, pheochromocytoma

being highly vascular and containing high intracellularwater, display high signal intensity on T2-weighted images[9]. MIBG imaging is very accurate for localizing pheo-chromocytomas with a specificity approaching 100%. Thehigh similarities in molecular structures of MIBG to nor-epinephrine allow it to be taken up by pheochromocytomatissue [10]. However, MIBG is negative in 15% of cases ofbenign pheochromocytoma and in up to 50% of malignantcases [11]. Therefore patients who are suspected to have a pheochromocytoma but have a negative MIBG scanshould be subjected to PET scan (18F-dopamine positronemission tomography) for confirmation and to rule outmalignancy or metastasis but this is currently not availablelocally [12].

Biochemical diagnosis of pheochromocytoma includesassessment of plasma free metanephrines which has a sen-sitivity of 99% and 24 hours urine fractionated meta-nephrines. Our results confirmed elevated plasma meta-nephrines but these should have been obtained followingmicturition or upon micturition attacks.

Other tests include plasma catecholamines and 24-hoururinary catecholamines, total metanephrines and vanillyl-mandelic acid but these have lower specificity [13]. In ourcase, urine catecholamines were within normal limits andthis can occur in urine paraganglioma especially if urinesample was not taken immediately following micturition[14-15].

Cystoscopy shows typically a submucosal nodule cov-ered by normal urothelium. It provides more qualitativedata about the tumor and its location especially if surgeryis being planned. Blood pressure fluctuations may occurduring cystoscopy, therefore care must be taken not toextensively irrigate the mass under high pressure duringthe procedure. Biopsies are not encouraged during cysto-scopy due to their low positive yield, high bleeding ten-dencies and risk of hypertensive crisis [2, 6].

Treatment of choice is partial cystectomy with com-plete excision of the lesion. Transurethral resection is con-traindicated mainly because of the high risk of precipitat-ing a hypertensive crisis and the elevated recurrence ratein case of incomplete resection [6]. Care must be taken toensure adequate pre-operative preparations in order tomake the surgery safer [16]. Chemotherapy and radiother-apy have limited effectiveness in the treatment of localrecurrence and metastatic disease [3].

CONCLUSION

Paragangliomas of the urinary bladder are rare. Patientsmight present with typical signs and symptoms but diag-nosis is sometimes achieved only after excision and histo-

logical examination of the tumor. It is recommended to doa clinical and biological assessment, plasma metaneph-rines being the biochemical test of choice due to its highsensitivity. Plasma metanephrines have to be measuredafter a micturition attack or ideally before and after mic-turition.

REFERENCES

1. Bhalani S, Casalino D, Manvar A. Paraganglioma of thebladder. The Journal of Urology 2011; 186: 279-80.

2. Dahm P, Gschwend JE. Malignant non-urothelial neo-plasms of the urinary bladder: a review. Eur Urol 2003;44: 672-81.

3. Whalen RK, Althausen AF, Daniels GH. Extra-adrenalpheochromocytoma. J Urol 1992; 147: 1-10.

4. Sweetser PM, Ohl DA, Thompson NW. Pheochromo-cytoma of the urinary bladder. Surgery 1991; 109: 677-81.

5. Wu JP: Wujieping’s Urology, 1st ed, Ji’nan: ShandongScience and Technology Press, 2003: 987-9.

6. Liu Y, Dong S, Dong Z, Mao X, Shi X. Diagnosis andtreatment of pheochromocytoma in urinary bladder. JZhejiang Univ Sci B 2007; 8 (6): 435-8

7. Alderazi Y, Yeh MW, Robinson BG et al. Pheochromo-cytoma: current concepts. Med J Aust 2005; 183: 201-4.

8. Seki N, Mukai S, Gamachi A, Migita T, Maeda K, Ogata N.A case of bladder pheochromocytoma. Urol Int 2001; 66(1): 57-60.

9. Warshawsky R, Bow SN, Waldbaum RS, Cintron J.Bladder pheochromocytoma with MR correlation. J ComptAssist Tomogr 1989; 13: 714-16.

10. Ma JX, Zhu RS, Yu JF, Ding CD, Jing CQ. The value ofdiagnosis of aberrant and (or) malignant pheochromocy-toma with 131I-MIBG imaging. Chinese Journal ofNuclear Medicine 1996; 16: 101-2.

11. Mehta N, Paniker V, Shah A. MIBG negative pheochro-mocytoma. JAPI March 2010 ; 58: 186-7.

12. Grassi I, Nanni C, Vicennati V et al. I-123 MIBG scintig-raphy and 68Ga-DOTANOC PET/CT negative but F-18DOPA PET/CT positive pheochromocytoma. Clin NuclMed 2011; 36: 124-6.

13. Onishi T, Sakata Y, Yonemura S, Suqimura Y. Pheochro-mocytoma of urinary bladder without typical symptoms.Int J Urol 2003; 10 (7): 398-400.

14. Doran F, Varinli S, Bayazit Y, Bal N, Özdemir S.Pheochromocytoma of the urinary bladder. APMIS 2002;110: 733-6.

15. Kappers MHW, van den Meiracker, Alwani RA, Kats E,Baggen MGA. Paraganglioma of the urinary bladder.Netherlands, The Journal of Medicine April 2008; 66 (4):163-5.

16. Pastor-Guzmán JM, López-García S, Giménez-Bachs JMet al. Paraganglioma of the bladder: controversy regard-ing treatment. Urol Int 2004; 73: 270-5.