Recurrent Malignant Pheochromocytoma with Lymph Nodal Metastasis in a Child: A Rare Case.

Malignant pheochromocytoma in children manifesting as local recurrence with multiple lymph nodal metastasis is a rare entity. We report a case of a 14-year-old child with recurrent sporadic malignant pheochromocytoma presenting 8 years after primary surgery with retroperitoneal lymphadenopathy. The child underwent excision of the tumor along with retroperitoneal lymphadenectomy. Histopathology confirmed pheochromocytoma with extensive lymph node metastasis. The patient has no signs of disease recurrence till date. This report supports the long-term follow-up and aggressive surgical approach to remove all foci of tumor in recurrent pheochromocytoma.

INTRODUCTION

Pheochromocytoma in children is rare with an incidence of 2/million.[1] The incidence of pediatric malignant pheochromocytoma is reported to be 10–50% of all pediatric pheochromocytomas.[2] There are only a few reports in children on the successful surgical management of malignant pheochromocytoma with lymph node metastases in the primary setting.[3] Furthermore, the treatment of such recurrent disease in the adrenal bed and in para-aortic lymph nodes is a difficult proposition. We report a rare case of a 14-year-old child with recurrent sporadic malignant pheochromocytoma who presented 8 years after left adrenalectomy for pheochromocytoma.

CASE REPORT

A 14-year-old child who underwent left adrenalectomy for pheochromocytoma originating in the left adrenal gland at the age of 6 years, presented to the emergency medical service with accelerated hypertension and blurring of vision. Ultrasonogram and magnetic resonance imaging showed a 4 cm × 3 cm recurrence in the left adrenal fossa with multiple para-aortic lymph nodes [Figure 1]. 131I-MIBG showed avid uptake at the same sites. The plasma-free normetanephrine was elevated (567 pg/ml) and serum cortisol was within normal limits. The fundus examination showed grade 4 hypertensive retinopathy. The primary histology was reported as having classical Zellballen pattern suggestive of pheochromocytoma without malignant features. Familial syndromes were ruled out. The preoperative preparation was performed with alpha adrenergic receptor blocker (prazosin 5 mg BD) followed by beta-adrenergic receptor blocker (propanol 20 mg BD) with high salt diet and liberal water intake. Laparotomy under general anesthesia was performed, and the tumor was excised along with retroperitoneal lymphadenectomy. The blood pressure of the child normalized on the 3rd postoperative day. The histopathology was suggestive of pheochromocytoma with extensive lymph node metastasis indicating malignant features [Figure 2]. The patient is now free of antihypertenive medications. Follow-up protocol included metabolic testing at 3 months and 1 year and computed tomography (CT) scan imaging at the end of 1st year. There is no evidence of disease recurrence in the child till date.

Figure 1

Coronal T2 Trufi magnetic resonance images of the abdomen show multiple lobulated T2 heterogeneous hyperintense lesions in the left adrenal bed and paravertebral region, closely abutting the medial border of the left kidney suggestive of recurrence in the left adrenal bed with para-aortic lymphadenopathy

Figure 2

Section shows tumor cells arranged in alveolar pattern surrounded by capillary-rich framework giving a characteristic Zellballen pattern. The periphery shows lymphoid tissue (H and E, ×40) (a). The cytoplasm is amphiphilic, granular, with round to ovoid nuclei, coarsely clumped chromatin, and prominent nucleoli (H and E, ×40) (b)

DISCUSSION

Malignant pheochromocytoma is defined as an occurrence of distant metastasis in nonchromaffin tissue and not by local invasion.[4] The incidence of malignancy among pediatric patients is higher as compared to adult population (47% vs. 10%–30%).[2] The typical sites of metastasis include bone, lung, liver, and lymph nodes. The risk factors for pediatric malignant pheochromocytoma include the extra-adrenal location, primary tumor >6 cm, sporadic nature, gland weight >250 g, and early onset postoperative hypertension.[2] The risk factors for recurrence are predominantly due to rupture of tumor capsule or incomplete tumor resection. The reported incidence of local tumor recurrence is 16%–26% after negative margins for primary surgery.[23] The incidence of recurrence following adrenal conserving surgery for the pheochromocytoma is reported to be 15%–20% and is almost similar to total adrenalectomy.[5] Positron emission tomography-CT with different radiopharmaceuticals has a significant role in the detection of metastasis when MIBG scintigraphy is negative.[6]

Surgical resection is the mainstay of treatment due to poor response to medical management. The role of laparoscopic surgery in this setting is limited to specialized centers with experienced laparoscopic surgeons. The overall 5-year and 10-year disease-specific survival rate for malignant pediatric pheochromocytoma is reported to be 78% and 31%, respectively.[2] The outcome of children with recurrent malignant pheochromocytoma is variable, with isolated reports of patients surviving more than two decades.[7] The possible explanation for the high survival rate among children may be due to tumor detection at an earlier age, less biologically aggressive tumor, and aggressive surgical management.[2] In cases of unresectable disease, surgical debulking and local therapies such as ablation or radiotherapy can provide effective palliation.[28] Radiolabelled MIBG (I131) or somatostatin analogs, separate or in synergistic combination, may achieve tumor volume control and partial hormonal response in 50% of the patients with metastatic pheochromocytoma.[9] The chemotherapeutic drugs have shown poor response rate in this setting.[29] The role of molecular targeted therapies such as m-TOR inhibitors, tyrosine kinase inhibitors, HER-2/neu inhibitors, and antiangiogenic agents are currently in trial setting only.[9]

Repeat metabolic testing should be performed 2–6 weeks after surgery. These patients require long-term annual biochemical follow-up. Subsequent imaging or MIBG scan is indicated only in the setting of elevated biochemical parameters.[10]

The occurrence of metastatic pheochromocytoma in lymph nodal tissue is extremely rare, and this makes our case unique. Although there are reports of lymph nodal recurrence in adult pheochromocytoma, to the best of our knowledge, it has not been documented in children.

In malignant pheochromocytoma, careful sustained clinical and biochemical follow-up is advocated as tumor recurrence may occur years after the initial surgery. In such children even with lymph nodal metastasis, aggressive surgical approach should be considered because it offers effective clinical and functional control of the disease as seen in our patient.

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Conflicts of interest

There are no conflicts of interest.