Abdominal Paraganglioma Associated With MEN 2A

A 48-year-old woman, with no known family history of MEN-2A syndrome, underwent surgery for a thyroid nodule in April 1989. Total thyroidectomy was performed and the pathology study defined a bilateral medullary thyroid cancer (MTC). Due to the possibility that the patient could be an RET mutation carrier, we ordered genetic studies, suprarenal CT, catecholamines in 24-h urine test and parathyroid study. Calcium, phosphorus and PTH were normal. A mild increase of metanephrines was detected in 24-h urine tests (metanephrines 640 μg/24 h; normal levels 60–350 μg/24 h) and suprarenal CT demonstrated the existence of bilateral suprarenal tumors (right, 1.5 cm; left, 2.5 cm). The genetic study confirmed the RET mutation: c.1901G > A (p.C634Y). Given these findings, bilateral suprarenalectomy was performed.

After 15 years of follow-up without incidents, a new increase in arterial pressure levels was detected along with an increase in 24 h urine catecholamine levels (noradrenaline, 140 μg/24 h (vn 12–86); adrenaline, 150 μg/24 h (vn 2–23); normetanephrine, 684 μg/24 h (vn 120–650); total metanephrine, 2444 μg/24 h (vn 180–1000); total catecholamine, 289 μg/24 h (vn 14–110); AVM, 25.6 mg/24 h (vn 1–10). Abdominal CT showed evidence of a mass with a hypodense center measuring 4.5 × 3 cm in the interaortocaval region above the left renal vein and in close contact with the vena cava (Fig. 1a). The findings of a metaiodobenzylguanidine (MIBG) scintigraphy were compatible with a mass showing increased uptake in the right suprarenal position suggestive of paraganglioma or right pheochromocytoma relapse (Fig. 1b).

Fig. 1.

(a) Abdominal CT: mass with a hypodense center measuring 4.5 × 3 cm in the interaortocaval region, above the left renal vein and in close contact with the vena cava. (b) MIBG: increased uptake of the mass in the right suprarenal position suggestive of right pheochromocytoma or paraganglioma recurrence. (c) Immunohistochemistry: positive for chromogranin A, sinaptofisin, enolase and vimentin. (d) Pathology: tumor with a surface surrounded by a fibrous pseudocapsule with evidence of ganglion cells inside.

The patient, who had previously been prepared with phenoxybenzamine, underwent surgery that revealed a tumor measuring 4–5 cm located in the area between the vena cava, left renal vein and aorta, which was completely removed. There were no post-OP complications, and catecholamine levels normalized. The pathology and immunohistochemistry studies of the surgical specimen reported a tumor measuring 5.5 × 4.5 × 2.5 cm surrounded by a fibrous pseudocapsule and evidence of ganglion cells in the interior with positive immunochemistry for chromogranin A, sinaptofisin, enolase and vimentin, compatible with paraganglioma (Fig. 1c–d). After this last surgery, the patient continued to be clinically asymptomatic with normal 24-h urine catecholamine.

MEN 2A is a rare disease that is associated with MTC in 100% of cases, pheochromocytoma in 50% and hyperparathyroidism in 10%–15% of cases.¹ The association of paragangliomas with MEN 2A is exceptional in the scientific literature published to date² (bibliographic search on Medline in February, 2011).

Extra-adrenal paraganglioma and pheochromocytomas are chromaffin-type tumors, 95% of which are located in the intra-abdominal area (fundamentally adrenal glands), 2%–4% in the thorax and 1% in the neck. Paragangliomas are usually located in the sympathetic chain ganglia, while extra-adrenal retroperitoneal paragangliomas have a poorer prognosis.² 20% of these paraganglioma are potentially malignant and are usually multicentric. They present a high rate of local recurrence or metastasis. This recurrence can appear years or decades after the resection of the primary tumor, and long-term follow-up is therefore necessary.³

The clinical manifestations are determined by the capacity of some paraganglioma (39%) to secrete hormones such as catecholamines, gastrin, thyrocalcitonin, ACTH, VIP and PTH, among others; arterial hypertension is the most common symptom.³ In the case that we describe, the elevated hormone and blood pressure levels led to the suspected diagnosis.

The diagnosis of pheochromocytomas and paragangliomas is based on proper anamnesis and physical examination together with the determination of plasma catecholamine and/or metanephrine levels in 24-h urine. The tumor can be located with techniques such as MIBG (which has the capability to detect tumors <0.5 cm, metastatic and multicentric tumors), CT, NMR or PET. These techniques are also used during the follow-up of these patients for the early diagnosis of possible recurrences. In the case that we present, MIBG and CT detected the existence of the tumor, while the definitive diagnosis was provided by the immunohistochemistry and histology studies.⁴

The surgical treatment of choice for pheochromocytomas is uni- or bilateral suprarenalectomy, and the laparoscopic approach is currently a safe procedure that provides good results. In the case of paragangliomas, surgical resection is the treatment of choice, accompanied by a complete examination of the abdominal and pelvic cavities in search of other tumors. In the case of our patient, no other affected areas were found. In malignant or metastatic pheochromocytomas, treatment can be associated with MIBG-I¹³¹ at high doses (200 mCi), and the doses may be repeated up to a total of 800–1200 mCi. An improvement in the size of the metastasis is seen in 50%, but complete remission is reached in only 4% of cases. The use of chemotherapy and/or radiotherapy does not improve the results of surgery and are used as palliative treatment in patients with advanced disease.⁵

To conclude, we should point out that the association of paragangliomas with MEN 2 is described in the scientific literature as being unusual and may be confused with the diagnosis of pheochromocytoma or with the lack of resolution of the lesion after surgical removal, and can reappear years later. Therefore, the long-term follow-up of these patients is essential due to the possible appearance of local recurrence, metastasis or, as in our case, associated paraganglioma. MIBG and the determination of catecholamines are the tests of choice.