Urinary bladder paraganglioma is a very rare tumor that arises from chromaffin cells of the sympathetic nervous system in the bladder wall [1]. Urinary bladder paraganglioma constitutes less than 0.5% of all bladder tumors and ~ 1% of all paragangliomas [2]. Among paragangliomas of the genitourinary tract, the urinary bladder is the most common site (~ 79.2%), which is followed by the urethra (~ 12.7%), renal pelvis (~ 4.9%), and ureter (~ 3.2%) [1]. Most of the bladder paragangliomas are seen in middle-aged adults and are common among females. Mostly, they have a benign clinical course, only ~ 10% turn to be malignant [3]. They can be functional or non-functional. Functional paragangliomas secrete excess catecholamines and will be symptomatic. Non-functional paraganglioma remains asymptomatic and is usually detected incidentally [4]. The typical presentation of bladder paraganglioma includes hematuria and symptoms induced by micturition due to increased catecholamine release, which includes hypertension, palpitation, and headache [5]. Non-functional bladder paraganglioma presents as painless hematuria or urinary tract obstruction [4]. The classical triad of bladder paraganglioma includes persistent hematuria, episodic hypertension, and post-micturition syncope, but this is rarely seen [3]. Even though sporadic, urinary bladder paraganglioma can occur familially or as part of syndromes like neurofibromatosis 1, von Hippel–Lindau syndrome, multiple endocrine neoplasias 2, and carney complex [2].
On imaging, bladder paraganglioma appears as a solid well-defined vascular lesion and is seen within the submucosal layer of the bladder [2]. Up to 40% are located in the dome and above the trigone of the bladder [6]. Non-functional bladder paraganglioma is commonly detected by ultrasound. On ultrasound, they appear as hypervascular echogenic mass and may have cystic foci within, representing areas of necrosis [3]. Paragangliomas are susceptible to degeneration and may show areas of necrosis, cystic changes, hemorrhage, and calcification [4]. On CT, it appears as soft tissue attenuation mass lesion, which shows homogeneous intense hyperenhancement on contrast study. It reflects the rich blood supply of paraganglioma. In the case of degeneration, heterogeneous enhancement is seen [1]. Areas of hemorrhage and calcification can also be seen [7]. On magnetic resonance imaging (MRI), the lesion shows multiple hyperintense foci interspersed with areas of signal voids, giving the classical salt and pepper appearance [1]. On T2-weighted imaging, the lesion demonstrates increased signal intensity due to the high vascularity and intracellular water content. It appears hyperintense on diffusion-weighted images also [2]. Even though MRI is most sensitive for detection, M-iodobenzyl-guanidine (MIBG) study is considered highly specific for paraganglioma, since it provides functional information [7]. But its use is limited because of restricted availability and being highly expensive [3]. Advanced functional imaging using somatostatin analogs has been used for early detection, staging, recurrence, and treatment assessment of these tumors. The new somatostatin analog PET molecules that have been developed include gallium-68-labeled-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptides. PET CT with Ga DOTA-NOC has been proven to be highly sensitive and specific for neuroendocrine tumors than diagnostic CT and scintigraphy [8]. Negative tracer uptake in paragangliomas is seen related to small lesion size due to partial volume effect, alteration of receptor expression due to prior chemotherapy, or due to low or absent somatostatin receptor expression as in our case [9].
Functional paragangliomas secrete catecholamines, and a 24-h assessment of urinary vanillylmandelic acid helps in the diagnosis. Non-functional paragangliomas do not secrete excess catecholamines, and henceforth, preoperative diagnosis is difficult. In such cases, diagnosis depends on histopathology and immunohistochemistry [10]. Histologically paragangliomas are composed of tumor cells arranged in a zellballen pattern with abundant granular eosinophilic cytoplasm separated by vascularized fibrous septae [11]. As in our case, most of the paragangliomas are synaptophysin and chromogranin positive, but negative for cytokeratin, which is the appropriate way to diagnose a non-functional paraganglioma [4].
The most common differential of urinary bladder paraganglioma is urothelial bladder carcinoma. It is commonly seen in the bladder base (~ 80%) and typically occurs in elderly men with occupational exposure to carcinogens and with a history of smoking [2]. The lesion margins are not well delineated, show uneven enhancement, and can invade the bladder wall and other local organs [4]. Leiomyomas are the most common mesenchymal tumor of the bladder accounting for ~ 35% of benign bladder tumors. It occurs commonly in young and middle-aged women. The lesion margins are well demarcated and show mild-to-moderate enhancement [4]. This lesion appears hypointense on T2-weighted imaging, which helps to differentiate from bladder paraganglioma. [2]. Rhabdomyosarcomas are the most common pediatric bladder tumor, with a high risk of malignancy, early metastasis, and poor prognosis. They present as grape-like lobulated mass with heterogeneous enhancement in the bladder base and mostly show local invasion [2]. Bladder hemangiomas can also be included in the differential of hypervascular lesions, but is common in the pediatric age group, and are commonly seen in the posterolateral wall of the bladder [2].
The treatment of choice is the surgical removal of the lesion, which includes transurethral resection and open/laparoscopic cystectomy (partial/radical). In the case of functioning tumors, strict control of blood pressure by administering alpha-blocker in the pre- and intraoperative period is necessary to prevent hypertensive crisis [3]. Recurrent cases are treated by radiotherapy. Chemotherapy does not have an important role except for metastatic disease [7]. Long-term follow-up is necessary for paraganglioma to detect recurrence and metastasis [3].
