Pheochromocytoma (PCC) is an exceptionally rare neoplasm in children, accounting for 1% of pediatric hypertensive patients [1]. Approximately 20% of PCC are found in the pediatric population [2,3]. PCC can arise either from adrenal or extra-adrenal ganglion. Tumors arising from the adrenal gland are known as PCC and those from the extra-adrenal locations are called PGL or paraganglioma [4]. Alhough there is some consistent literature about their clinical presentation, long term follow-up studies on pediatric PCC are not available [2,5-10]. The recently delineated genetic screening strategies are often not within reach of the general population in developing countries [11,12]. The aim of this study was to investigate the clinical presentation and outcome of surgery in children with PCC presenting at a tertiary care center in a developing country.

Statistical analysis was done using SPSS software version 13.0. Mann-Whitney and Chi-squared tests were used where applicable and 2-tailed P values of less than 0.05 were considered significant.

The proportion of pediatric PCC in our center was 16% (24/150). Among familial group, two had MEN-2A and one had MEN-2B syndromes with co-existent medullary thyroid carcinoma (MTC). Child with MEN-2B was normotensive and PCC was diagnosed by routine biochemical screening. Two other children with bilateral adrenal PCC on follow-up were found to have a sibling each who also had adrenal PCC. One of these children had presented with synchronous bilateral PCC and other with metachronous bilateral PCC after 9 years of follow-up. All the extra-adrenal PCC were located in the abdomen. The lone malignant tumor was located in the organ of Zukerkandl and was metastatic (liver) at presentation.

Characteristics of children with PCC are summarized in Table I. The findings in familial and sporadic groups were comparable. A total of 29 tumours were removed from 24 children. Only one child received phenoxybenzamine whereas all the others received prazocin for pre-operative preparation. Laparoscopic resection was successful in a quarter of cases. Total adrenalectomy was performed in all but one child with bilateral PCC where cortical sparing adrenalectomy was done. There was no peri-operative mortality.

TABLE I  Comparison of Familial and Sporadic Pediatric Pheochromocytoma

Clinical presentation of pediatric PCC and incidence of bilateral PCC in the current study was in accordance with the published literature [3,5-10]. However, incidence of familial disease, extra-adrenal PCC and malignancy was low and mean tumor size was more in our study. We could find only two studies published such from India so far [9,10]. Centers, that routinely perform genetic testing report high incidence of familial pediatric PCC that ranges from 30-70% [1,2,8,11,12]. Restricted availability and affordability of genetic testing are the main reasons for low incidence of familial PCC in our study. Low incidence of malignancy and extra-adrenal PCC seem to be inter-related as extra-adrenal PCC are more likely to be malignant than adrenal PCC. However, the reason for diagnosing lesser number of extra-adrenal PCC by Indian centers is difficult to explain [9,10].

The two main limitations of the current study are the possibility of underestimating incidence of genetic disease because routine genetic screening was not performed, and secondly, the short duration of follow-up. Familial PCC may sometimes take a decade to manifest, as was also evident in one of our cases. We had earlier reported clinicopathological profile of 5 pediatric PCC [15]. In the subsequent decade we managed 19 more patients. With dedicated follow-up of these patients we could detect two familial cases. Despite all the limitation and for the fact that mean tumor size was large in our series, the outcome of surgery in our study was comparable to the previous reports.

Early diagnosis and intervention are important for the successful management of this rare pediatric neoplasm. Routine genetic screening of these children is mandatory for the detection and timely management of familial PCC. However, importance of good history taking and long- term follow up cannot be overemphasized. These children should be managed by a multidisciplinary team consisting of pediatricians, endocrinologists, endocrine surgeons, genetic counselors and anaesthetists, who have experience in managing these cases on regular basis.

1. Armstrong R, Sridhar M, Greenhalgh KL, Howell L, Jones C, Landes C, et al. Phaeochromocytoma in children. Arch Dis Child. 2008;93:899-904.

2. Caty MG, Coran AG, Geagen M, Thompson NW. Current diagnosis and treatment of pheochromocytoma in children. Experience with 22 consecutive tumors in 14 patients. Arch Surg. 1990;125:978-81.

3. Ludwig AD, Feig DI, Brandt ML, Hicks MJ, Fitch ME, Cass DL. Recent advances in the diagnosis and treatment of pheochromocytoma in children. Am J Surg. 2007;194: 792-6.

4. Delellis RA, Llyod RV, Heitz PU, Eng C, eds. Pathology and genetics of tumors of endocrine organs Lyon, France: IARC Press.

5. Reddy VS, O’Neill JA, Jr., Holcomb GW 3rd, Neblett WW 3rd, Pietsch JB, Morgan WM, 3rd, et al. Twenty-five-year surgical experience with pheochromocytoma in children. Am Surg. 2000;66:1085-91.

6. Ciftci AO, Tanyel FC, Senocak ME, Buyukpamukcu N. Pheochromocytoma in children. J Pediatr Surg. 2001;36:447-52.

7. Kim HY, Lee HS, Jung SE, Lee SC, Park KW, Kim WK. Experience with surgical excision in childhood pheochromocytoma. J Korean Med Sci. 2004;19:401-6.

8. Pham TH, Moir C, Thompson GB, Zarroug AE, Hamner CE, Farley D, et al. Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center. Pediatrics. 2006;118:1109-17

9. Bhansali A, Rajput R, Behra A, Rao KL, Khandelwal N, Radotra BD. Childhood sporadic pheochromocytoma: clinical profile and outcome in 19 patients. J Pediatr Endocrinol Metab. 2006;19:749-56.

10. Ganesh HK, Acharya SV, Goerge J, Bandgar TR, Menon PS, Shah NS. Pheochromocytoma in children and adolescents. Indian J Pediatr. 2009;76:1151-3

11. Pacak K, Eisenhofer G, Ahlman H, Bornstein SR, Gimenez-Roqueplo AP, Grossman AB, et al. Pheochromocytoma: Recommendations for Clinical Practice from the First International Symposium. Nat Clin Pract Endocrinol Metab. 2007;3:92-102.

12. Karagiannis A, Mikhailidis DP, Athyros VG, Harsoulis F. Pheochromocytoma: an update on genetics and management. Endocr Relat Cancer. 2007;14:935-56.

13. Petri BJ, van Eijck CH, de Herder WW, Wagner A, de Krijger RR. Phaeochromocytomas and sympathetic paragangliomas. Br J Surg. 2009;96:1381-92.

14. Khafagi FA, Shapiro B, Fischer M, Sisson JC, Hutchinson R, Beierwaltes WH. Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine. Eur J Nucl Med. 1991;18:191-8.