A 53-year-old female patient initially presented with hoarseness and no other symptoms 3 years prior, leading to the diagnosis of a left jugular foramen mass at a local hospital. Subsequent evaluation confirmed a GJT and the patient underwent transarterial embolization (TAE). Following TAE, the patient's hoarseness showed no significant clinical improvement. However, because the patient was informed by the treating physician that surgical resection carried a high risk of damaging the posterior cranial nerves and a substantial likelihood of permanent dysphagia, surgical resection was deferred.

At 1 month before admission to Sanbo Brain Hospital (Beijing, China), the patient developed dysphagia, progressive left lower limb weakness and somnolence. Neurological examination revealed left-sided sensorineural hearing loss (cranial nerve VIII deficit, with a duration of ~1 year), left facial hypoesthesia (impaired pain and light touch perception; cranial nerve V deficit, with a duration of ~1 year), incomplete left eyelid closure, ipsilateral nasolabial fold flattening, leftward uvular deviation (progressive cranial nerve VII deficit, ultimately presenting as House-Brackmann grade IV (26), with a duration of ~6 months), diminished left gag reflex and left tongue deviation on protrusion (cranial nerves IX, X and XII deficits, with a duration of ~1 month). Left lower extremity motor strength was graded 4/5 (with a duration of ~1 month). The patient's medical history included 6 months hypertension managed with oral nifedipine. Notably, during the patient's prior hospitalization, the blood pressure remained stable without signs suggestive of pheochromocytoma (27).

Contrast-enhanced MRI demonstrated a 65-mm dumbbell-shaped tumor centered in the left jugular foramen, extending into the cerebellopontine angle (CPA). The lesion compressed the brainstem, cerebellum and fourth ventricle, resulting in obstructive hydrocephalus (Figs. 1A, S1A and SB). Radiological classification was Fisch type D2(28) and Glasscock-Jackson type IV (29). Bone-window CT revealed jugular foramen and carotid canal erosion (Fig. 1B). Adrenal CT and echocardiography showed no abnormalities (Fig. S1C).

Given the stable blood pressure on admission, the absence of hypertensive episodes during prior interventions, and most importantly, insufficient awareness of the occult secretory potential in such rare tumors, the catecholamine secretory nature of the tumor was not initially recognized. Consequently, biochemical testing was omitted.

A multidisciplinary team (neurosurgery, neurointerventional radiology, anesthesiology, neurocritical care and nutrition) collaboratively optimized preoperative management. Given the hypervascularity of the tumor, preoperative embolization was performed (25,30). External ventricular drainage was additionally placed to mitigate intracranial pressure.

Post-embolization 24-h urinary catecholamines were found to be elevated: Epinephrine, 53.53 µg/24 h (normal range, 0-21), norepinephrine, 138.93 µg/24 h (normal range, 0-80) and dopamine 281.67 µg/24 h (normal range, 0-400). Plasma levels similarly showed marked norepinephrine elevation (2,247.60 pg/ml; normal range, 70-750, supine), confirming ectopic catecholamine secretion (31,32). Post-resection normalization (norepinephrine, 70.80 pg/ml) validated the diagnosis.

Under local anesthesia, diagnostic angiography was performed to confirm the vascular supply of the tumor, originating from the left external carotid, internal carotid and vertebral arteries (Fig. 1C). The use of local anesthesia at this stage allowed continuous neurological assessment and informed the subsequent decision to proceed with general anesthesia for definitive embolization. Balloon occlusion testing of the internal carotid artery confirmed adequate collateral circulation through the anterior communicating artery (Fig. S1G). Following general anesthesia induction, super-selective embolization of feeders from the posterior auricular, occipital meningeal and ascending pharyngeal arteries achieved >90% devascularization (Fig. 1C).

Notably, contrast administration during angiography triggered hypertensive crises (180/100 mmHg), persisting for 15 min. A second surge (220/130 mmHg) occurred during embolization, necessitating intravenous nicardipine (administered as an intravenous bolus of 0.5 mg, followed immediately by continuous intravenous infusion at a maintenance dose of 1-5 mg/h, titrated according to blood pressure), a first-line antihypertensive agent for intraoperative hypotensive anesthesia and catecholamine-induced hypertension (which was recommended in current guidelines and literature) (33,34), to rapidly stabilize hemodynamics (Fig. 2A).

Based on the specific characteristics of the patient's condition, literature review (Table I) and accumulated clinical experience, a multidisciplinary team discussion was conducted to formulate a meticulous surgical plan: Given the tumor's compression of cranial nerves and the brainstem, early surgical excision was recommended, with tumor resection attempted on day 3 following interventional embolization. α/β-adrenergic blockers and magnesium sulfate injections were prepared for intraoperative use, where the anesthesiology team managed the patient's condition in accordance with the real-time anesthetic course.

Following induction of general anesthesia with stable hemodynamic monitoring (Fig. S1C), the surgical team initiated a two-phase approach. A periumbilical incision first provided autologous adipose tissue for subsequent reconstruction. A standardized retroauricular C-shaped incision was then extended along the left neck, permitting systematic exposure of the sternocleidomastoid muscle, internal jugular vein (IJV) and internal carotid artery (ICA). The tumor presented a bimodal configuration: i) An intraluminal IJV component extending caudally to C4; and ii) a deep extravenous portion nestled between the ICA anteriorly and vertebral artery posteriorly. Mastoidectomy with facial nerve canal decompression (preserving petrous, tympanic and labyrinthine segments) and sigmoid sinus skeletonization preceded intracranial access. The intracranial extension of the tumor demonstrated CPA involvement with middle ear extension, displaying characteristic hypervascular, grayish-red morphology adherent to the facial nerve's petrous segment.

Extracranial tumor resection. After complete exposure, sequential vascular control was achieved through IJV and facial vein ligation. Meticulous microsurgical technique facilitated circumferential dissection of tumor from the cervical ICA (including vertical and partial horizontal segments). Jugular foramen decompression enabled en bloc resection of the petrous portion, with intraoperative hemostasis maintained by using an absorbable gelatin sponge compression during tumor debulking (Fig. S2).

Intracranial tumor resection. The intracranial portion of the tumor was primarily located in the left side of the CPA area, with its surface covered by proliferative pathological blood vessels. The trigeminal nerve was displaced superiorly by the tumor, whilst the facial and vestibulocochlear nerves were compressed ventrally and inferiorly. The tumor was tightly adhered to the brainstem but was ultimately resected in segments after sufficient decompression. Surrounding tissues were preserved intact. Adipose tissue was used to fill the jugular foramen area for structural support (Fig. S2).

Anesthetic management process. Prior to surgery, the anesthesiologist had prepared a comprehensive treatment plan for the potential massive catecholamine release, including the use of α-adrenergic blocker (phenoxybenzamine), which were ultimately not administered due to concerns about the risk of hypotension. During the surgical procedure, β-adrenergic antagonists (landiolol) and calcium channel blockers (nicardipine) were used for maintaining stable heart rate and blood pressure. Throughout the procedure, blood pressure remained stable and there were no episodes of sudden or uncontrollable hypertension (Fig. 2B).

Intraoperative management. Postoperatively, the patient received treatment in the intensive care unit and was able to breathe spontaneously ~8 h after surgery, leading to the removal of the endotracheal tube. On the following day, the patient was transferred back to a general ward without experiencing hypotension or hypoglycemia due to reduced plasma catecholamine levels. The posterior cranial nerve symptoms did not worsen postoperatively and they continued to receive nutrition through the gastric tube that had been inserted prior to surgery. In total, 20 days after the operation, there was an improvement in the posterior cranial nerve symptoms and limb muscle strength, allowing for a smooth discharge from the hospital. After returning home, the patient continued nasogastric tube feeding, rested at home and gradually recovered. Subsequently, 1 month postoperatively, the patient was able to eat orally and manage daily activities independently.

Formalin-fixed, paraffin-embedded tissue sections (4 µm) were processed using a VENTANA automated immunostainer following the manufacturer's protocols. Antigen retrieval was performed with CC1 buffer (pH 8.0) at 95˚C for 24 min. Primary antibodies were incubated at 37˚C for 32 min, followed by HRP-labeled secondary antibody and DAB detection. Sections were counterstained with hematoxylin. Microscopy was performed on a Leica MD3000 microscope. Antibody dilutions of 1:100-1:500 were applied.

H&E and IHC staining revealed the classic structure of paragangliomas and their immunomarkers. H&E staining observations: Tumor cells exhibited a nest-like and trabecular distribution of tumor cells, with the cell nests separated by abundant thin-walled and reticular blood vessels, accompanied by focal necrosis (Fig. 2C).

IHC staining observations were as follows: Synaptophysin(+), tumor protein 53)(-), microtubule-associated protein(-), myelin basic protein(-), chromogranin A(+), neuron-specific enolase(+), CD31(-), coagulation factor VII(-), S-100 protein(focally positive), vimentin(+), neuronal nuclei(-), CD34(-), SRY-box transcription factor 10(focally positive), histone H3 trimethylated at lysine 27(+), epithelial membrane antigen(-), CD56(+), glial fibrillary acidic protein(-), oligodendrocyte transcription factor 2(-), epidermal growth factor receptor(-), succinate dehydrogenase B(+), neurofilament(focally positive) and Ki-67 (proliferation marker; positive in <1% of tumor cells).