Bilateral Adrenal Neuroblastoma is Different

Abstract

Background/Aims: Bilateral adrenal neuroblastoma is rare and can be due to multifocal primary or contralateral metastasis. Staging is confusing in these patients and treatment guidelines are difficult to set. The present study examines the clinical, biological and therapeutic features of bilateral adrenal neuroblastoma. Methods: We identified 4 cases primarily located in both adrenals out of 148 neuroblastomas treated between 1992 and 2006. We studied the clinicopathological findings and biological features, including MYCN amplification, and analyzed the treatment strategies and results. Results: All patients were younger than 6 months of age and all had multiple liver metastases. Three had subcutaneous nodules and massive liver enlargement. All underwent chemotherapy prior to operation. Two babies had large bilateral tumors without preservable glands and underwent bilateral adrenalectomy. Both had MYCN gene amplification and died of widespread (brain and bone) metastases some weeks later. In the remaining two patients adrenalectomy was performed on the side of the larger tumor with tumor enucleation on the other side to preserve hormonal function followed by 2 courses of mild chemotherapy in one patient. These tumors were not amplified. Both of these children are doing well. Conclusions: Bilateral adrenal neuroblastomas fit neither into stage 4 s nor into stage 4. Their clinical behavior is exceptional with a number of multicystic forms, variable MYCN amplification, widespread metastases and a high mortality. Bilateral adrenalectomy is sometimes unavoidable, but unilateral removal with contralateral enucleation, partial resection or observation are valid alternatives. Mortality is higher than in regular stage 4 s cases. This particular group of neuroblastomas required individually tailored therapeutic strategies based on the size, extent and prognostic markers.

neuroblastoma - adrenal - bilateral - MYCN amplification - metastases

References

• 1 Beckwith J B, Perrin E V. In situ neuroblastomas: a contribution to the natural history of neural crest tumors.  Am J Pathol. 1963;  43 1089-1104
• 2 Berrebi D, Lebras M N, Belarbi N, Couturier J, Fattet S, Faye A, Peuchmaur M, de Lagausie P. Bilateral adrenal neuroblastoma and nephroblastoma occurring synchronously in a child with Fanconi's anemia and VACTERL syndrome.  J Pediatr Surg. 2006;  41 e11-e14
• 3 Cassady C, Winters W D. Bilateral cystic neuroblastoma: imaging features and differential diagnoses.  Pediatr Radiol. 1997;  27 758-759
• 4 Chan E L, Harris R E, Emery K H, Gelfand M J, Collins M H, Gruppo R A. Favorable histology, MYCN-amplified 4S neonatal neuroblastoma.  Pediatr Blood Cancer. 2007;  48 479-482
• 5 Duzovali O, Ozer C, Turhan A H, Arslankoylu A E, Yilgor E, Polat A, Aksoyek S. Bilateral adrenal cystic neuroblastoma with massive hepatomegaly and intracystic hemorrhage.  Pediatr Blood Cancer. 2005;  44 525-526
• 6 Gonzalez-Crussi F, Hsueh W. Bilateral adrenal ganglioneuroblastoma with neuromelanin. Clinical and pathologic observations.  Cancer. 1988;  61 1159-1166
• 7 Hachitanda Y, Ishimoto K, Hata J, Shimada H. One hundred neuroblastomas detected through a mass screening system in Japan.  Cancer. 1994;  74 3223-3226
• 8 Hiyama E, Yokoyama T, Hiyama K, Yamaoka H, Matsuura Y, Nishimura S, Ueda K. Multifocal neuroblastoma: biologic behavior and surgical aspects.  Cancer. 2000;  88 1955-1963
• 9 Ikeda H, Suzuki N, Takahashi A, Kuroiwa M, Nagashima K, Tsuchida Y, Matsuyama S. Surgical treatment of neuroblastomas in infants under 12 months of age.  J Pediatr Surg. 1998;  33 1246-1250
• 10 Ishiguro Y, Iio K, Seo T, Nagaya M, Ito T. Bilateral adrenal neuroblastoma.  Eur J Pediatr Surg. 1994;  4 37-39
• 11 Kawaguchi F, Nakada K, Kitagawa H, Fujioka T, Kim Y, Enami T, Kuwabara M, Wakisaka M, Yamate N, Chihara H. et al . An infant with bilateral adrenal neuroblastoma found by mass-screening: report of a case.  Surg Today. 1993;  23 546-550
• 12 Koksal Y, Varan A, Kale G, Tanyel F C, Buyukpamukcu M. Bilateral adrenal cystic neuroblastoma with hepatic and splenic involvement in a newborn.  J Pediatr Hematol Oncol. 2005;  27 670-671
• 13 Kramer S A, Bradford W D, Anderson E E. Bilateral adrenal neuroblastoma.  Cancer. 1980;  45 2208-2212
• 14 Lee S Y, Chuang J H, Huang C B, Hsiao C C, Wan Y L, Ng S H, Lee T Y, Ko S F. Congenital bilateral cystic neuroblastoma with liver metastases and massive intracystic haemorrhage.  Br J Radiol. 1998;  71 1205-1207
• 15 Park W S, Chi J G. Bilateral neuroblastoma in situ associated with microcephaly.  J Korean Med Sci. 1993;  8 99-103
• 16 Pinarli F G, Danaci M, Tander B, Dagdemir A, Diren B, Acar S, Rizalar R. Bilateral adrenal cystic neuroblastoma with superior vena cava syndrome and massive intracystic haemorrhage.  Pediatr Radiol. 2004;  34 746-749
• 17 Shaw A, Sabio H. Bilateral adrenal neuroblastoma.  Am J Pediatr Hematol Oncol. 1984;  6 41-43
• 18 Shimada H, Ambros I M, Dehner L P, Hata J, Joshi V V, Roald B. Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee.  Cancer. 1999;  86 349-363
• 19 Stovroff M, Dykes F, Teague W G. The complete spectrum of neurocristopathy in an infant with congenital hypoventilation, Hirschsprung's disease, and neuroblastoma.  J Pediatr Surg. 1995;  30 1218-1221
• 20 Suzuki H, Honzumi M, Funada M, Tomiyama H. Metachronous bilateral adrenal neuroblastoma.  Cancer. 1985;  56 1490-1492
• 21 Tonini G P, Boni L, Pession A, Rogers D, Iolascon A, Basso G, Cordero di Montezemolo L, Casale F, Perri P, Mazzocco K, Scaruffi P, Lo Cunsolo C, Marchese N, Milanaccio C, Conte M, Bruzzi P, De Bernardi B. MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4 s: the Italian experience with 295 children.  J Clin Oncol. 1997;  15 85-93
• 22 Yanai T, Okazaki T, Yamataka A, Fujita H, Saito M, Lane G, Yamashiro Y, Miyano T. A rare case of bilateral stage IV adrenal neuroblastoma with multiple skin metastases in a neonate: diagnosis, management, and outcome.  J Pediatr Surg. 2004;  39 1782-1783
• 23 Zaizen Y, Suita S, Yamanaka K, Nagoshi M, Tsuda T. Bilateral adrenal neuroblastoma.  Eur J Pediatr Surg. 1997;  7 304-307