Paragangliomas, also known as extra-adrenal pheochromocytomas, arise from neural crest-derived neuroendocrine cells. These tumors are rare, with an incidence of 0.04 to 0.95 cases per 100,000 [1]. They frequently originate along the sympathetic chain, are predominantly intra-abdominal, and often secrete catecholamines. Paragangliomas may also arise from parasympathetic nerves in the head and neck, which are typically non-secretory in nature. Approximately 30%-50% of paragangliomas are familial, and 20% have metastatic potential [2].

The organ of Zuckerkandl (OZ), a common site for abdominal paragangliomas, is located near the origin of the inferior mesenteric artery (IMA) or at the aortic bifurcation [1]. Surgical resection remains the mainstay of treatment, but reports describing resections involving major vascular structures are scarce [3].

We report a case of a 50-year-old man with a large OZ paraganglioma infiltrating the aorta, inferior vena cava (IVC), and surrounding structures, necessitating a complex en bloc resection and vascular reconstruction. Retrospective case reports are exempted from Institutional Review Board approval as per institutional guidelines. Informed consent was obtained from the patient for the publication. This study adheres to the principles of the Helsinki Declaration of 1964.

A 50-year-old hypertensive man presented with abdominal pain. A contrast-enhanced computed tomography (CECT) scan of the abdomen and pelvis revealed a retroperitoneal mass measuring 5.3×6.2×8.3 cm with necrosis and coarse calcifications, extending from the L1 to L3 vertebral levels and displacing the left ureter. The tumor encased the infrarenal aorta, its bifurcation, the left common iliac artery, and the IMA (Fig. 1). It also involved the distal IVC and the bifurcation of the left common iliac vein (Fig. 2).

Figure 1. Mass infiltrating the aorta and its bifurcation, along with the left common iliac artery bifurcation and left psoas muscle. (A) Coronal section, (B) axial section.

Figure 2. Mass infiltrating the IVC at its bifurcation. (A) Coronal section, (B) axial section. IVC, inferior vena cava.

Biochemical tests revealed elevated 24-hour urinary metanephrines and vanillylmandelic acid levels, consistent with a diagnosis of paraganglioma. A CT-guided biopsy confirmed the diagnosis. Neck ultrasonography showed a normal thyroid gland, and a chest CT scan was negative for metastasis.

The patient was scheduled for surgical resection. Due to tumor infiltration of the aorta and IVC, an en bloc resection of the tumor and affected vessels was planned. Preoperative optimization included alpha-blockade with phenoxybenzamine, followed by beta-blockade with metoprolol to achieve blood pressure control. These measures were initiated two weeks before surgery.

A midline laparotomy was performed. The ascending and descending colons were mobilized, and the root of the mesentery was incised from the ileocecal junction to the duodenojejunal flexure to expose the IVC, aorta, and tumor in the retroperitoneum. Intraoperatively, a predominantly left-sided mass was observed, extending cranially from just below the left renal artery to the mid-portion of the left common iliac artery and vein. The mass encased the aorta, the origin of the IMA, aortic bifurcation, and the left common iliac artery. It also infiltrated the left common iliac vein, confluence of the common iliac veins, and adjacent distal IVC, extending posteriorly into the left psoas major muscle and abutting the anterior longitudinal ligament without infiltration. The left ureter was uninvolved (Fig. 3). Tumor dissection from the vascular structures was not attempted due to extensive vascular infiltration. Instead, the tumor was mobilized from its retroperitoneal and soft tissue attachments, leaving it tethered to the major vessels.

Figure 3. Intraoperative view of the mass.

Proximal vascular control of the aorta and IVC was achieved just below the renal artery and veins, respectively. Distal control was established on the right side at the level of the right common iliac artery and vein and on the left side at the level of the left internal and external iliac arteries and veins. The left internal iliac artery and vein were ligated at the bifurcation of the left common iliac vessels.

Intraoperative heparinization was initiated with 5,000 IU of unfractionated heparin, administered 3 minutes before clamping. Vascular clamps were applied proximally and distally. An en bloc resection of the tumor was performed along with the left psoas major muscle, aorta, IVC, left common iliac artery, and left common iliac vein. Vascular reconstruction was performed using a bifurcating Dacron Y-graft: the infrarenal aorta was reconstructed to the right common iliac artery and left external iliac artery, and the infrarenal IVC was reconstructed to the right common iliac vein and left external iliac vein (Fig. 4). The total clamping time was 60 minutes. Hemostasis and distal perfusion were confirmed after reconstruction, and distal pulses were monitored using Doppler imaging as described by Shah et al. [4].

Figure 4. Vascular reconstruction with bifurcated Dacron Y-grafts.

Postoperatively, the mean arterial pressure was maintained above 80 mmHg. The patient was started on anticoagulation (rivaroxaban 5 mg twice daily) and antiplatelet therapy (aspirin 75 mg once daily) on the day of surgery, consistent with the protocol described by Shah et al. [4], and was advised to continue these medications for life [5].

Histopathological examination confirmed the diagnosis of paraganglioma, measuring 10.0×9.0×5.0 cm. The IVC contained a tumor thrombus infiltrating both the IVC and the aorta, with an intraluminal component. Lymphatic tumor emboli were present, but the vessel margins were free of tumor. The Ki-67 index was <10%.

A postoperative CT angiogram confirmed graft patency and anastomotic integrity, with no evidence of leakage (Fig. 5). A Gallium-68 dotate, Tyr3-octreotate positron emission tomography (⁶⁸Ga-DOTATATE PET) scan, performed 6 months after surgery, showed no evidence of metastasis. At the 6-month follow-up, the patient remained disease-free, and a Doppler ultrasound confirmed a patent graft with no thrombus formation.

Figure 5. Postoperative computed tomography angiography showing patent arterial reconstruction.

Paragangliomas of the OZ are rare neuroendocrine tumors that predominantly secrete norepinephrine, leading to symptoms of catecholamine excess. These tumors can be aggressive, with a high propensity for metastatic spread. Given the rarity of this disease, our understanding of its natural history remains limited [1]. Among OZ paragangliomas, 77% are functioning tumors, typically presenting with hypertension, headache, and palpitations, while non-functioning tumors (23%) manifest less specifically, with symptoms like abdominal pain or a palpable mass in approximately 32% of cases [6].

Common imaging modalities used for the metastatic evaluation of paragangliomas include metaiodobenzylguanidine (MIBG) scintigraphy and ⁶⁸Ga-DOTATATE PET scan. The reported sensitivity of the MIBG scintigraphy for detecting paragangliomas is 67% [6]. In contrast, ⁶⁸Ga-DOTATATE PET scan has a sensitivity of 80% and a positive predictive value of 62% [6]. ⁶⁸Ga-DOTATATE PET is considered the first-line imaging modality in the following situations: (1) patients suspected to have paraganglioma, (2) high-risk patients, such as those screened for carriers with familial paraganglioma syndromes, and (3) patients with metastatic disease, particularly with bone involvement [6].

There are no definitive histological criteria to define the malignancy of paragangliomas. Indicators of malignancy include invasion of adjacent tissues, capsular invasion, elevated mitotic rate, tumor size >5 cm, weight >80 g, recurrence, and distant metastasis [7]. Retroperitoneal paragangliomas present with synchronous metastasis in approximately 10% of patients, and up to 40% develop metastases over the disease course, most commonly to the lungs, lymph nodes, bones, and spleen [8].

Currently, no standardized guidelines exist for the surgical management of paragangliomas. For OZ paragangliomas, an initial attempt should be made to resect only the retroperitoneal tumor before deciding to perform en bloc vascular resection. However, complete surgical excision remains the mainstay of treatment, even if vascular resection is required [9]. Approximately 150 cases of OZ paragangliomas have been reported in the literature [9]. However, none of these cases have documented an approach requiring en bloc resection of the aorta, IVC, and their bifurcation, along with the psoas muscle, as was necessary in this case.

The challenges in such surgeries include achieving adequate proximal and distal vascular control, which requires detailed anatomical orientation and knowledge of collateral development. The availability of vascular surgeons and appropriate grafts for reconstruction plays a critical role in ensuring anastomotic integrity. Clamping time, intraoperative heparinization, and post-operative management are also key factors influencing outcomes, as described by Raja and Malik [10]. The choice of anticoagulation therapy depends on the type of vascular reconstruction. Arterial reconstruction requires antiplatelet therapy, while venous reconstruction necessitates anticoagulation. The preferred antiplatelet agent is aspirin (75 mg once daily). Direct oral anticoagulants are increasingly used due to their ease of administration and reduced monitoring requirements compared to unfractionated heparin or warfarin. However, the optimal duration of antithrombotic therapy remains uncertain due to limited data. In this case, given the use of a Dacron graft for both arterial and venous reconstruction, the patient was prescribed lifelong anticoagulation and antiplatelet therapy [5].

Postoperative vascular complications, such as anastomotic leakage, venous graft thrombus leading to deep venous thrombosis or pulmonary embolism, and arterial graft occlusion causing limb ischemia, must be anticipated. Successful treatment benchmarks include normalized plasma or urinary levels of fractionated metanephrines and catecholamines, negative imaging findings, and stable blood pressure. Follow-up should include biochemical markers monitoring and imaging every 6 months for the first three years, followed by annual surveillance thereafter. For vascular reconstructions, Doppler studies every three months during the first year and annual imaging with CT or magnetic resonance imaging are recommended to monitor graft patency and detect recurrence or metastasis [6].

There is a <10% risk of local recurrence following complete resection, which usually occurs 5 to 15 years after surgery. Approximately 15% to 25% of patients with recurrence experience distant metastases, with 5-year overall survival rates for metastatic disease ranging from 50% to 70% [7].

OZ paragangliomas are particularly prone to vascular invasion due to their anatomical proximity to major vessels. However, literature on vascular resection in OZ paragangliomas remains limited (Table 1). Dossett et al. [11] reported a malignant OZ paraganglioma invading the aorta and IVC that required en bloc resection, with arterial reconstruction using a bifurcated Dacron graft and venous reconstruction using a tube Dacron graft. Stevenson et al. [12] described an OZ paraganglioma with left iliofemoral venous thrombosis, requiring aortic resection and reconstruction with a Y-graft, as well as ligation of the left iliac vein. Wang et al. [13] reported resection of the infrarenal aorta and IVC with expanded polytetrafluoroethylene grafts reconstruction in a para-aortic paraganglioma. Teter et al. [14] described three patients, including two with OZ paragangliomas and one with recurrent pheochromocytoma, requiring various vascular resections and reconstructions. Tagaya et al. [15] reported a laparoscopic resection of an OZ paraganglioma with IMA resection.

Table 1 . Vascular resection in the paraganglioma of the OZ: reported cases in the literature, including present case.

	Age (y)	Sex	Tumor size (cm)	Location	Vessel involved	Procedure performed	Reconstruction
Dossett et al. [11]	46	Male	4.5×3.7	OZ	IVC, aorta, right distal ureter	Resection of distal infrarenal aorta and IVC with right nephroureterectomy	Dacron Y-graft for aorta; Dacron tube graft for IVC
Stevenson et al. [12]	46	Male	9×9	OZ	Aortic bifurcation with Proximal common iliac arteries	Resection of aortic bifurcation and proximal common iliac arteries	Y-graft for aorta
Wang et al. [13]	56	Female	9.5×6.5	OZ	Infrarenal IVC, aorta; 8 cm segment	Resection of infrarenal aorta and IVC	ePTFE tube graft for aorta and IVC
Teter et al. [14]	73	Female	4.6×4.3	OZ	Distal infrarenal aorta and its bifurcation	Resection of distal infrarenal aorta with bilateral proximal common iliac arteries	Dacron Y graft for aorta (aortobifemoral bypass)
Teter et al. [14]	45	Female	7.3×6.3	OZ	Anterior wall of distal infrarenal IVC and right common iliac artery	Resection of a portion of the anterior wall of distal infrarenal IVC and right common iliac artery	Primary repair for IVC; 8 mm ringed ePTFE graft for right common iliac artery
Tagaya et al. [15]	47	Male	NA	OZ	IMA	Laparoscopic resection of IMA	NA
Present case	50	Male	10.0×9.0×5.0	OZ	Infrarenal aorta, IVC with its bifurcation	Resection of infrarenal aorta and IVC with its bifurcation; ligation of the left internal iliac artery and vein	Dacron Y-graft for aorta; Dacron Y-graft for IVC

OZ, Organ of Zuckerkandl; IVC, inferior vena cava; IMA, inferior mesenteric artery; ePTFE, expanded polytetrafluoroethylene; NA, not applicable..

Lifelong follow-up is essential, as recurrence can occur decades after surgery. The 5-year survival rate after resection is 75%, whereas the 10-year disease-free survival rate drops to 45%. Recurrence is common, occurring in more than half of successfully treated cases. Thus, radical excision is critical to achieving long-term disease-free survival [16].

While resections involving the aorta, IVC, and psoas muscle have been described in other malignancies, such as retroperitoneal lymph node dissection for nonseminomatous germ cell tumors [10,17], this case represents the first reported OZ paraganglioma requiring combined resection and reconstruction of the aorta, IVC, and the bifurcation of both vessels. The procedure involved resection of the infrarenal aorta, IVC, and left psoas muscle, followed by Dacron Y-graft reconstruction of both vessels, which can be classified as Type 2 vascular involvement, as per Shah et al. [4].

In summnary, this case illustrates the significant surgical challenges associated with managing a large OZ paraganglioma with extensive vascular involvement. The successful en bloc resection and vascular reconstruction underscore the importance of meticulous surgical planning and interdisciplinary collaboration. Given the tumor’s potential for aggressive behavior and recurrence, careful postoperative monitoring of biochemical markers and imaging is essential for the early detection of any recurrence. This case reinforces that complete surgical excision remains the cornerstone of treatment for paragangliomas, as chemotherapy or radiation therapy have not demonstrated significant survival benefits.

None.

The authors have nothing to disclose.

Concept and design: all authors. Analysis and interpretation: SSK, SM. Data collection: SSK. Writing the article: SSK, SM, AR. Critical revision of the article: AR. Final approval of the article: AR. Statistical analysis: SSK, AR. Obtained funding: none. Overall responsibility: AR.