The unseen storm: Intraoperative catecholamine crisis revealing a silent bladder paraganglioma

Abstract

Bladder paraganglioma is a rare neuroendocrine tumor that may remain clinically silent and present unexpectedly during surgery. We report a 63-year-old woman with non-specific urinary urgency and frequency found to have a bladder mass. During transurethral resection, severe hypertensive crisis and uncontrollable bleeding occurred, necessitating conversion to open partial cystectomy. Histopathology and immunohistochemistry confirmed bladder paraganglioma with muscularis propria invasion and a low proliferative index. This case highlights the importance of considering paraganglioma in vascular bladder tumors to prevent life-threatening intraoperative complications.

1. Introduction

Paragangliomas of the urinary bladder are exceedingly rare, accounting for less than 0.06% of all bladder tumors.¹ They arise from chromaffin cells of the sympathetic plexus in the bladder wall. Due to their potential to secrete catecholamines, manipulation during cystoscopy or TURBT can provoke profound hypertension, tachycardia, or even cardiac arrest.^2,3 This case is presented for its exemplary demonstration of this classic intraoperative complication and the critical role of histopathologic and immunohistochemical confirmation,^4,5 highlighting the importance of preoperative suspicion for this rare entity. While the classic triad of symptoms (headache, palpitations, and sweating) is well described, the majority of bladder paragangliomas present with non-specific urinary symptoms, leading to a dangerous diagnostic blind spot. This report exemplifies the most dramatic consequence of this diagnostic blind spot: an unanticipated intraoperative catecholamine storm. It also highlights the decisive multidisciplinary management that prevented a fatal outcome.

2. Case presentation

A 63-year-old female presented with non-specific irritative urinary symptoms, including urgency and frequency. She denied hematuria, obstructive urinary symptoms, nocturia, fever, bone pain, weight loss, or loss of appetite. Her past medical history was significant for type 2 diabetes mellitus with poor glycemic control (HbA1c: 7.9%) and hypothyroidism. She had no known drug allergies. There was no family history of endocrine disorders or malignancy. She was a non-smoker with a history of secondhand smoke exposure and denied alcohol use.

On physical examination, her vital signs were stable, with a blood pressure of 130/75 mmHg and a pulse rate of 90 beats per minute. Her body mass index was 31 kg/m². Cardiovascular examination was unremarkable, and both electrocardiography and echocardiography showed normal findings.

Laboratory investigations revealed normal complete blood count and coagulation profile. Renal function tests were within normal limits. Glycemic markers were elevated, consistent with her known diabetes mellitus. Liver function tests were normal except for a mildly elevated alkaline phosphatase level (273 U/L). Pelvic ultrasound and magnetic resonance imaging demonstrated an intravesical mass measuring approximately 19–20 mm on imaging, which appeared larger (approximately 4 cm in maximal diameter) during cystoscopy, located on the left posterolateral wall and dome of the bladder, with no radiological evidence of local invasion or lymphadenopathy.

The patient underwent planned transurethral resection of bladder tumor under spinal anesthesia. Cystoscopic evaluation revealed a large, highly vascular and actively bleeding mass measuring approximately 4 cm on the left posterolateral wall and dome of the bladder (Fig. 1). Shortly after initiation of tumor resection, the patient developed a sudden and severe hypertensive crisis accompanied by uncontrollable bleeding, precluding safe continuation of the procedure.

Fig. 1.

Cystoscopic evaluation revealed a large, highly vascular and actively bleeding mass measuring approximately 4 cm on the left posterolateral wall and dome of the bladder (Fig. 1).

Given the intraoperative instability, the procedure was converted to an open partial cystectomy via a lower midline incision. The tumor was excised with an approximately 1 cm margin, and the bladder was closed in two layers with placement of a surgical drain.

Histopathological examination with hematoxylin and eosin staining revealed features consistent with paraganglioma, including invasion into the muscularis propria, without evidence of lymphovascular or perineural invasion (Fig. 2, Fig. 3). Immunohistochemical analysis confirmed the diagnosis, demonstrating strong positivity for synaptophysin and chromogranin within tumor cells, S100 positivity highlighting sustentacular cells, and a low Ki-67 proliferation index of less than 1%. Carcinoembryonic antigen staining was negative (Fig. 4). The final diagnosis was bladder paraganglioma.

Fig. 2.

Histopathologic findings of the bladder tumor.

(A) Low-power hematoxylin and eosin staining ( × 40) demonstrating the classic nested “zellballen” architecture.

(B) Tumor infiltration into the muscularis propria ( × 100).

Fig. 3.

High-power histopathologic examination.

(A) Hematoxylin and eosin staining ( × 200) showing tumor cells with abundant granular cytoplasm.

(B) Round nuclei without significant atypia ( × 200).

Fig. 4.

Immunohistochemical features of the tumor.

(A) Strong and diffuse cytoplasmic positivity for synaptophysin and chromogranin A in tumor cells, confirming neuroendocrine differentiation ( × 200).

(B) S100 immunostaining highlighting the peripheral sustentacular cells, characteristic of the classic zellballen growth pattern ( × 100).

This report epitomizes a critical diagnostic and surgical challenge in urology: the clinically silent bladder paraganglioma. The patient's initial presentation with non-specific irritative voiding symptoms, devoid of classic catecholamine-excess signs, perfectly illustrates the primary diagnostic pitfall associated with these tumors.^1,6 The sentinel intraoperative event—a severe hypertensive crisis upon tumor manipulation—was a characteristic manifestation of acute catecholamine release, transforming a routine procedure into a life-threatening emergency.^2,3

The definitive diagnosis hinged on comprehensive histopathologic evaluation. While hematoxylin and eosin staining suggested the possibility, immunohistochemistry provided incontrovertible confirmation, which is the diagnostic cornerstone for neuroendocrine tumors.^4,5 The classic immunoprofile—strong diffuse positivity for synaptophysin and chromogranin within the tumor cells, coupled with S100 positivity highlighting the peripheral sustentacular cells—is diagnostic of paraganglioma. The low Ki-67 proliferative index (<1%) further suggests an indolent biological behavior, a favorable prognostic feature.⁷

Mechanical compression of the tumor during TURBT triggered a massive catecholamine discharge, leading to intense vasoconstriction and likely contributing to uncontrollable bleeding from the highly vascular tumor bed.^2,8 This sequence validates the established management guideline: when a paraganglioma is suspected, mandatory preoperative preparation with alpha-adrenergic blockade for 10–14 days is required.^3,9

For paragangliomas, malignant potential is determined solely by the presence of metastatic disease or local recurrence rather than local invasion alone.^1,10 Given this risk and the potential for hereditary syndromes, lifelong follow-up with periodic biochemical testing and cross-sectional imaging is recommended.^9,10

This case report has inherent limitations. Its retrospective, single-case nature limits the generalizability of the findings. Most notably, preoperative biochemical screening for catecholamine excess was not performed due to the complete absence of suggestive symptoms. This very omission, however, crystallizes the report's core message: the profound danger of the "silent" paraganglioma. It highlights the practical dilemma urologists face and argues for a more proactive screening approach in ambiguous cases.

3. Conclusions

This report illustrates a classic presentation of a rare disease, where the intraoperative complication was the key diagnostic clue. This case serves as a critical reminder for urologists to:

• 1.Maintain a high index of suspicion for paraganglioma in the differential diagnosis of any bladder mass, especially those with atypical presentation.^1,6
• 2.Elicit a careful history for symptoms of catecholamine excess and consider preoperative biochemical screening for high-risk cases.^3,9
• 3.Be prepared to manage acute hemodynamic instability and convert to open surgery if necessary, as the team's swift decision was pivotal in this successful outcome.

Therefore, cultivating a high index of suspicion for this rare entity is not merely an academic exercise, but a crucial defensive strategy in the urologist's armamentarium to prevent potentially fatal intraoperative complications.

CRediT authorship contribution statement

Mehdi Komaki: Investigation, Methodology, Writing – review & editing. Khadijeh Askari: Formal analysis, Investigation, Resources, Writing – review & editing. Reza Shamsollahi: Conceptualization, Data curation, Investigation, Methodology, Supervision, Writing – original draft, Writing – review & editing.