Left subdiaphragmatic paraganglioma supplied by contralateral right renal artery

Abstract

INTRODUCTION

Paragangliomas are neuroendocrine tumors of the autonomic nervous system that arise from neural crest cells. Paragangliomas are typically extra-adrenal, non-functional and can be discovered incidentally, posing diagnostic and therapeutic challenges.

PRESENTATION OF CASE

We present the unusual case of a young man who presented with an acute abdomen secondary to small bowel obstruction, and was found to have an incidental left-sided subdiaphragmatic paraganglioma supplied by a branch of the contralateral right renal artery.

DISCUSSION

Emergent laparotomy revealed an internal hernia as the source of the small bowel obstruction. Initial attempts to remove an incidental left subdiaphragmatic mass were aborted because of bleeding. Subsequently, after preoperative superselective embolization of the feeding vessel arising from the right renal artery, the mass was successfully resected. Pathology was consistent with a paraganglioma.

CONCLUSION

This report highlights the rarity of the location and blood supply of an incidental left subdiaphragmatic paraganglioma found in the setting of a small bowel obstruction.

1. Introduction

Paragangliomas are rare neuroendocrine tumors of the autonomic nervous system that, similar to pheochromocytomas, arise from embryonic neural crest cells. However, while pheochromocytomas are by definition intra-adrenal and typically functional (i.e. secrete catecholamines), paragangliomas are extra-adrenal, found anywhere there is sympathetic ganglia, and are usually non-functional.¹

Intra-abdominal paragangliomas are most likely to be located at the organ of Zuckerkandl, a prominence of ganglion cells near the aortic bifurcation. However, because of their potential to grow from any extra-adrenal chromaffin tissue, unusual sites of origin are often recognized.^2–9 Nonetheless, to our knowledge there has been no report of specifically a subdiaphragmatic location, nor one with a feeding vessel that crosses the midline. To provide insight in to the management of this disease process, we present the unusual case of a young man with a unique paraganglioma that was incidentally discovered in the setting of acute abdominal pain.

2. Presentation of case

A 24 year old Hispanic male presented to the emergency department with acute, severe left-sided abdominal pain. Pain was intermittent, spastic, gradually increasing and localizing to the left upper quadrant. Symptoms of nausea, vomiting, diarrhea, flushing, palpitations, or weight loss were absent. The patient's medical history was unremarkable. Vital signs were within normal limits. Physical examination showed abdominal distension, diffuse abdominal pain with tenderness predominantly in the left upper quadrant suggestive of localized peritonitis. Laboratory tests where unremarkable, as well as an abdominal ultrasound and X-ray. However, a computed tomography (CT) scan of the abdomen showed the presence of a fixed loop of jejunum, and the possibility of midgut volvulus. Additionally, the scan demonstrated a 4.4 cm heterogeneous, markedly hypervascular mass, located superior to the third segment of the left hepatic lobe with a poor separation plane with the diaphragm (Fig. 1A–D). An emergent exploratory laparotomy was performed; it revealed an incarcerated internal jejunal hernia without evidence of necrosis, and a 15 cm × 1 cm inflamed appendix. Pathologic evaluation of the appendix demonstrated suppurative appendicitis and no evidence of malignancy. Following adhesiolysis, hernia reduction, and appendectomy, the subdiaphragmatic mass was exposed. The mass was attached to the underside of the diaphragm on the left side near the costal cartilage; it was non adherent to the liver. Upon manipulation of the mass, there was no elevation of blood pressure, but there was a strong pulse within the mass. An attempt at biopsy was aborted due to excessive bleeding from the mass. Once the bleeding was controlled, the decision to terminate the operation was taken in order further evaluate the mass postoperatively. With uneventful recovery from the initial operation, arteriography was performed on postoperative day six. Angiography revealed that the mass was supplied by a branch off the right renal artery (Fig. 2). To minimize blood loss and facilitate resection, preoperative superselective embolization of the vessel arising from the right renal artery that supplied the lesion was performed. The patient tolerated the embolization well and was re-operated on two days later. Upon re-exploration, the mass was intimately involved with the left diaphragm and pericardium. The mass was resected along with a peripheral 1 cm margin of diaphragm and pericardium. Closure of the diaphragm and pericardium was performed with running 3–0 polypropylene sutures (Figs. 3 and 4). The patient had an uneventful post-operative recovery and was discharged home six days after the second operation.

Fig. 1.

Thoraco-abdominal computed tomography. Panels A and B = Axial and lateral computed tomography scan image with intravenous contrast showing the tumor (T) adjacent to the liver (L) and abdominal wall. Panel C = Three dimensional reconstructed image showing tumor (T) in contiguity to the upper third segment of the left hepatic lobe. Panel D = Coronal computed tomography scan image showing the tumor (T) adjacent to left ventricle (LV).

Fig. 2.

Abdominal arteriography. Aorta (Ao), right renal artery (RRA), feeding artery off the right renal artery bifurcation (Arrows), left renal artery (LRA), common hepatic artery (CHA).

Fig. 3.

Intraoperative view. Tumor (T) is seen between diaphragma (DH) and liver (L). Abdominal wall (AW).

Fig. 4.

Macroscopic pathology. Tumor described as irregular shape, soft, brown and measured at 5.42 cm × 4.2 cm × 3.2 cm.

Upon pathological evaluation, the mass was consistent with a paraganglioma (Fig. 5 and Table 1). The surgical margins were negative, but the neoplastic growth showed rupture of the capsule and invasion to the surrounding soft tissues, as well as florid vascular invasion. Despite the former features, the mitotic count was low.

Fig. 5.

Microscopic pathology. Panel A = High powered field showing compact nest of polygonal cells, with highly vascular stroma. Cells with ovoid nuclei, granular chromatin, small eosinophilic nucleoli with mild reactive atypia, and a broad cytoplasm. Panel B = Low powered field showing extra-adrenal paraganglioma surrounded by capsule of dense fibroconnective tissue in continuity with striated muscle fibers.

Table 1.

Tumor immunohistochemistry.

Tumor marker	% of Staining
Chromogranin	35%
Neuronal Specific Enolase	40%
Protein S100	20%
Synaptophysin	<20%
CD34	35%

3. Discussion

Since their recognition in 1906, there have been many reports of unusual paraganglioma locations: bladder,² retroperitoneal,³ mediastinum,⁴ thyroid,⁵ ovary,⁶ prostate,⁷ gallbladder,⁸ and lungs.⁹ This is not surprising as tumors from neural crest cells origin can be found anywhere along the sympathetic chain. Interestingly, in our case the 5.5 cm subdiaphragmatic tumor was not in a location where one would normally expect to find sympathetic ganglia; a paraganglioma was not at the top of the pre-operative differential diagnosis of the hypervascular mass seen on CT scan. We humbly recognize that the lack of preemptive awareness that the mass in question could have been a catecholamine-secreting tumor placed our patient at substantial treatment related risks. Though the patient did well, we might have done things differently and this case report attempts to crystallize the insight into the treatment of this rare condition, and highlight the necessary preventive actions that can help avoid or decrease such potential treatment associated risks.

Paragangliomas are classified as either functional or non-functional according to the presence or absence of vasoactive catecholamine hormonal secretion; hence autonomic signs and symptoms such as hypertension, tachycardia, and diaphoresis are the most frequent clinical manifestation of a functional or active paraganglioma.¹ However, the majority of paragangliomas are discovered incidentally or due to mass effect. Similar to our case presentation, Erickson et al. found that 27% of incidental paragangliomas required pathological examination of the resected tissue before the diagnosis could be confirmed.¹⁰ Because non-functional paragangliomas or pheochromocytomas can become symptomatic upon intravenous contrast administration,¹² anesthesia,¹³ surgical manipulation,^12,13 and preoperative embolization,¹⁴ it is controversial whether pharmacologic adrenergic blockade is warranted in such instances.¹³ The North American Neuroendocrine Tumor Society (NANETS) consensus guidelines mention that all patients with pheochromocytoma or paraganglioma (even those with apparent normal levels of catecholamines) should receive appropriate preoperative medical management to block the effect of released catecholamines.¹⁵ Due to the acute nature of the initial presentation of the patient presented herein, and the unawareness of the etiology of the mass, the patient did not receive adrenergic blockade prior to surgical manipulation. Fortunately, the tumor did not produce catecholamines despite being exposed to many risk factors known to exacerbate hormonal secretion. Not having a high-index of suspicion for a paraganglioma in this situation and further manipulating the mass without appropriate pre-operative pharmacologic blockade is potentially fraught with hazard. Attempted resection of most hypervascular masses should be deferred until biochemical and better radiographic information is available. If there is the slightest index of suspicion for a paraganglioma, pre-operative pharmacologic blockade should be instituted because its benefits outweigh the risks.

Complete surgical resection is the treatment of choice for pheochromocytomas and paragangliomas. Laparoscopic surgery, in experienced hands, is now becoming the technique of first choice for the resection of adrenal tumors.¹⁵ The laparoscopic approach decreases post-operatively morbidity, hospital stay, and expense as compared with the conventional transabdominal technique,¹⁵ and decreases adhesion formation.¹⁶ However, the resection of paragangliomas through a laparoscopic approach is not as well established due to concerns of increased risk of malignancy compared to adrenal pheochromocytomas, and also because of the association of paragangliomas with major vascular structures such as the inferior vena cava and aorta, which increases the technical complexity of the operation.¹⁷ Because the patient in our case report presented emergently with an acute abdomen and the suspicion for a paraganglioma was low, we defaulted to an open abdominal exploration. Furthermore, because the repeat operation was performed eight days from the initial exploration, an open exploration remained the best choice as the window for adhesion formation was still favorable. We recognize that during the first operation, capsular disruption by open biopsy could have caused tumor spillage; we agree that basic oncologic principles should be followed to avoid compromising further therapy, but tissue diagnosis may allow clinicians to better diagnose, stage, and treat our patients. Though capsular and vascular invasion have historically been recognized as features concerning for malignancy, Rosai¹⁸ recently suggested that a high mitotic count and low reactivity for neuropeptides according to the immunohistochemistry pattern, are better predictors of malignancy. According to these new criteria, our patient is considered at low risk for recurrence, despite having had tumor extension into adjacent structures.

Though paragangliomas are usually sporadic, single tumors, they can be associated with hereditary syndromes, and be multifocal.¹² Certainly, the young age of our patient raises the possibility of a hereditary component, and though he lacks a family history of endocrine tumors, genetic testing should be considered. The patient deferred genetic testing. We know of no reports or associations of mid-gut volvulus,¹¹ appendicitis, and paragangliomas. Therefore, we believe that this paraganglioma was found incidentally in the setting of a rare combination of entities.

Though preoperative embolization as a treatment adjunct to the resection of paragangliomas can be beneficial, its practice remains controversial as it can lead to devastating consequences. Paragangliomas have a rich blood supply and preoperative embolization has been used successfully mostly for paragangliomas of the head and neck,¹⁹ though its use in intra-abdominal paragangliomas has also been reported.²⁰ Superselective catheterization techniques and intratumoral embolization techniques confer additional benefits in that they allow the embolization of more specific feeders, or even after direct puncture of the tumor (intratumoral embolization), resulting in decreased blood loss and operative time.²⁰ Others, however, have argued that in some cases there is no benefit from pre-operative embolization, demonstrating similar operative times and blood transfusion requirements. Therefore, the benefits of pre-operative embolization should be weighed on a case-by-case basis against the added risks of stroke, bleeding, and other thromboembolic complications.^19,20 Specifically, one should not perform a preoperative embolization of a known paraganglioma prior to performing an appropriate pharmacological blockade as it can lead to a catecholamine crisis and cardiovascular collapse.

4. Conclusion

This interesting case illustrates that paragangliomas, though a rare disease entity can occur in almost any possible anatomical position. A high index of suspicion for a paraganglioma should be present when any highly vascularized mass is found, as surgical manipulation or preoperative embolization can lead to devastating consequences if hormonal secretion is stimulated without adequate pre-operative adrenergic blockade. Because many of these tumors are found incidentally giving physicians the luxury of time, a careful and thorough preoperative workup should always be undertaken prior to attempting a biopsy or rushing to the operating room, as failure to do so can put patients at unnecessary risk.

Conflict of interest

No potential conflicts of interest exist.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient for publication of this case report and accompanying images. The Mayo Clinic Institutional Review Board deemed this study to be exempt because the patient presented in this case report is the first author of the manuscript.

Author contribution

JDM and BZ were involved in the conception and design of the study. JDM, BZ, JP, JPSL, SSL, FMS and DRF were involved in the analysis and interpretation of the study. JDM, BZ and JPSL wrote the article. JDM, BZ, JPSL, JP, SSL, FMS and DRF did critical revision of the study. JDM, BZ, JPSL, JP, SSL, FMS and DRF were responsible for final approval. JDM, JPSL and FMS collected the data. JDM and JPSL did the literature search.