Open abdominal aortic aneurysm repair with incidental finding of an extra-adrenal pheochromocytoma of the organ of Zuckerkandl

Introduction

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. The most common location of these tumors is within the adrenal medulla, where approximately 80–85% of pheochromocytomas arise. Extra-adrenal pheochromocytomas (EAPs), also known as paragangliomas, account for 15–20% of these tumors and may occur in any portion of the paraganglion system. The most common location of EAPs is at the organ of Zuckerkandl, which is a collection of chromaffin cells near the origin of the inferior mesenteric artery.^1,2 Here, we present a case of an EAP of the organ of Zuckerkandl incidentally discovered and resected during urgent repair of a symptomatic abdominal aortic aneurysm (AAA).

Case report

We herein report a case of a 66-year-old male who presented to a local hospital with a 6-h history of acute unrelenting left flank, abdominal, and lower back pain. Informed consent has been obtained from the patient for publication of the case report and accompanying images. The patient had a past medical history of poorly controlled hypertension, managed with carvedilol and spironolactone, as well as a 12-pack-year smoking history. At presentation, his blood pressure was elevated at 208/121 mmHg. On examination, a >6 cm AAA was tender to palpation. Abdominal computed tomography (CTA) demonstrated a juxtarenal 6.7 cm AAA with bilateral common iliac artery aneurysms. A 6-cm homogenous ill-defined mass was present anterior to the infrarenal AAA (Figure 1).

OPEN IN VIEWER

Figure 1.

CTA scan showing 67 mm juxtarenal AAA and anterior wall 60 mm homogenous mass anterior to the aorta.

The patient was subsequently transferred to our institution, where he emergently underwent an open AAA resection with aorto-bifemoral reconstruction. A transabdominal approach was taken to expose the aorta. After mobilizing the small bowel to the right, a 5–6-cm soft retroperitoneal mass was encountered anterior to the AAA and juxtaposed to the IMA origin (Figure 2). This mass was loosely attached to the anterior wall of the AAA and had a distinctly different appearance from the aneurysm. The mass was carefully dissected free, mobilized, and feeding vessels ligated. The 5.4 × 4.1 × 2.4 cm specimen was passed off the field. After resection of the mass, the patient’s blood pressure transiently dropped and responded to crystalloid resuscitation. The remainder of the open juxta renal AAA repair was completed without incident.

OPEN IN VIEWER

Figure 2.

Intraoperative photo demonstrating EAP of the organ of Zuckerkandl located anterior to the aneurysm.

Pathologic examination of the surgical specimen demonstrated a yellow, lobulated soft tissue mass, and frozen sectioning revealed a well-demarcated gray to red, variegated lesion with extensive hemorrhage (Figure 3). Immunohistochemical staining was positive for synaptophysin and chromogranin and negative for inhibin; these features were consistent with a pheochromocytoma. After surgery, the patient endorsed that his blood pressure had been very difficult to control for several years. In the last 12 months, he had experienced right-sided frontal headaches and increased irritability. Additionally, a family history was present as his father had undergone an adrenalectomy for labile blood pressure. The endocrinology service initiated a comprehensive work-up of the pheochromocytoma and evaluated for multiple endocrine neoplasia (MEN) syndrome. Following surgery, the patient’s 24-h urine fractionated metanephrines and catecholamines, calcium, calcitonin, parathyroid hormone, and vitamin D levels were all within normal limits. The surgical oncology service recommended an elective gallium-68 positron emission tomography (PET) and CT scan to evaluate for any residual disease; these studies were negative for residual local disease and metastatic disease.

OPEN IN VIEWER

Figure 3.

Pathologic examination of surgical specimen demonstrating a yellow, lobulated soft tissue mass; frozen sectioning revealed a well-demarcated gray to red lesion with extensive hemorrhage.

The patient’s post-operative course was unremarkable. His blood pressure remained well-controlled throughout his hospital course while on a single agent. He was discharged home on post-operative day 7.

Discussion

Pheochromocytomas are catecholamine-producing neuroendocrine tumors that are responsible for 0.1–0.6% of cases of secondary hypertension. Approximately 80–85% of these tumors arise within the adrenal medulla, whereas 15–20% are extra-adrenal and may be referred to as paragangliomas.^1,2 Most EAPs occur below the diaphragm, most commonly at the organ of Zuckerkandl, the collection of para-aortic chromaffin tissue just below the origin of the inferior mesenteric artery.^3,4

The classic symptoms of pheochromocytoma result from episodic release of excess catecholamines into the circulation leading to paroxysmal attacks of headaches, palpitations, anxiety, and diaphoresis. ⁵ Seventy-seven percent of EAPs of the organ of Zuckerkandl are clinically functioning and may present with the above symptoms. Seventy-four percent of patients with these tumors have hypertension. ⁶

Pheochromocytomas may be sporadic or associated with genetic syndromes such as multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, and von Hippel-Lindau syndrome. Diagnosis is typically confirmed with biochemical tests of hormonal excess by measuring serum or urine levels of catecholamines (dopamine, norepinephrine, and epinephrine) or their metabolites (normetanephrine and metanephrine). This is followed by anatomic localization by computed tomography (CT) or magnetic resonance imaging. If these fail to locate the tumor, functional localization may be attained using metaiodobenzylguanidine (MIBG) scintigraphy or PET. ⁵

The incidence of malignancy in EAPs is two to four times greater than the often quoted 10% for pheochromocytomas. The largest case review of 135 cases demonstrated that 41% of the EAPs of the organ of Zuckerkandl are malignant. Because it is difficult to pathologically differentiate benign and malignant tumors, malignancy is based on the presence of metastases. These tumors appear to spread via the lymphatic and hematogenic routes, with the most common sites of distant metastases being the bone, liver, and lungs. ⁶

Surgical resection is the recommended treatment for pheochromocytomas and EAPs, which are curable in >90% of patients.^6,7 For EAPs of the organ of Zuckerkandl, in particular, traditional treatment involves open surgical excision, though there have been several reports describing laparoscopic resection of these lesions.^8,9 Prior to planned surgical resection, the patient should be pharmacologically optimized with a goal of controlling the blood pressure and heart rate, preventing surgery-related catecholamine excess, and correcting volume contraction secondary to chronic vasoconstriction associated with excess catecholamines. ⁵ Alpha-receptor antagonists such as phenoxybenzamine are the initial drug of choice for management of hypertension. Beta-blockers should never be initiated prior to alpha-blockade because this will cause unopposed alpha-mediated vasoconstriction and may lead to acute cardiac insufficiency and pulmonary edema. However, they may be necessary following initiation of alpha-blockade to counteract tachy-arrhythmias, angina, and symptoms of excess catecholamines. More recently, calcium channel blockers have been demonstrated to be effective as primary therapy for blood pressure control or as adjuncts to alpha antagonists. Finally, to counteract the hypotension that may result from the initiation of alpha-blockade, patients are instructed to increase their fluid and salt intake with supplementation by intravenous crystalloids and colloids if this is insufficient.^5,7

In our patient’s case, the urgent nature of his presentation precluded a comprehensive work-up of the para-aortic mass prior to taking him to the operating room for repair of his symptomatic AAA. Additionally, because the patient’s aneurysm was juxtarenal, he was not a candidate for endovascular repair. Only one other case report exists in the literature describing an EAP of the organ of Zuckerkandl that was simultaneously resected during open infrarenal AAA repair. In that case, the patient presented with symptoms of abdominal and back pain for a year with exam concerning for an AAA. CT scan demonstrated an aortic aneurysm with a well-circumscribed tumor involving the anterior wall. Similar to our case, evaluation of the mass was not performed prior to urgent open AAA repair and concomitant resection of the mass, which was later pathologically confirmed to be a pheochromocytoma. ¹⁰

There are several case reports in the literature of concomitant adrenal pheochromocytomas and AAAs, leading to speculation that persistently elevated catecholamines contribute to AAA development and rupture. In two cases, ruptured AAA repair was complicated by intra-operative and post-operative blood pressure derangements with subsequent diagnosis of pheochromocytoma.^11,12 Thompson et al. ¹³ described the diagnosis of a pheochromocytoma with MIBG imaging after a repaired AAA began leaking. Kota et al. ¹⁴ reported a case of an incidentally discovered AAA on imaging for work-up of pheochromocytoma. Gupta et al. ¹⁵ reported a case of a biochemically silent right adrenal nodule discovered on CT evaluation of an AAA, which led to hypertensive crisis during induction of anesthesia. Fath et al. ¹⁶ discovered an ascending aortic aneurysm as well as a thoracoabdominal aortic aneurysm in a patient simultaneously diagnosed with a left adrenal pheochromocytoma.

Three cases of elective pheochromocytoma resection and concomitant AAA repair have been described.^17–19 In these cases, the patients were pre-operatively diagnosed with pheochromocytomas with imaging studies demonstrating a thoracoabdominal aortic aneurysm in one case and an infrarenal AAA in the other two. None of the patients were candidates for endovascular repair of their aortic aneurysms secondary to occlusive iliac disease and/or inappropriate neck morphology. Therefore, they all underwent planned open adrenalectomy and AAA repair in the same setting after pre-operative pharmacologic optimization with alpha-blockers and other anti-hypertensives.

Conclusion

Concomitant pheochromocytomas and AAAs are rare, with a small number described in the literature. Here, we describe the second case of simultaneous EAP of the organ of Zuckerkandl and AAA repair in the literature. Both cases demonstrate that these lesions can be urgently resected in the same setting as AAA repair. However, the lack of pre-operative pharmacologic optimization in a patient with a functional EAP may expose the patient to significant peri-operative hemodynamic instability and hypertensive crises. If these tumors are incidentally encountered, the anesthesia team should be forewarned of the potential complications prior to surgical manipulation and resection. Once a post-operative diagnosis of pheochromocytoma is made, a biochemical assessment and further imaging work-up should be performed to rule out residual or metastatic disease. If, on the other hand, these tumors are diagnosed pre-operatively, and there is no urgency to AAA repair, the appropriate diagnostic work-up for pheochromocytoma must be undertaken followed by the initiation of pharmacologic therapy to counteract the effects of excessive catecholamines. Subsequently, the pheochromocytoma can be resected either prior to, or concomitantly with, AAA repair.