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Neuroblastoma (NBL)

Neuroblastoma, an embryonal cancer of neural crest origin, shows metastases frequently at diagnosis.

Delloye-Bourgeois and colleagues demonstrate that neuroblastoma cell lines and patient-derived xenografts engraft and adopt a metastatic program in chick embryos. They identify Sema3C as a candidate switch that regulates metastatic spread 1).


Is the most malignant tumor in children and most common solid tumor in infants accounting for 8-10% of all childhood malignancies (about 8.7 million/year). It affects primarily children younger than 10 years of age. About 50% are below the age of 2 years. It occurs more frequently in boys than in girls (1.2:1). It originates from the neural crest cell, which normally gives rise to the adrenal medulla and sympathetic ganglia anywhere from the neck to the pelvis. It occurs in the abdomen in about 70% of cases (45% in adrenal medulla and 25% in sympathetic ganglia) 2).


NBL consists of nests of neuroblasts (undifferentiated small round cells) separated by fine fibrovascular septa (stroma) and showing Rosette formation in about one-third of cases. In about 5-10% of cases, some neuroblasts show differentiation into mature ganglion cells and the tumor is classified as ganglioneuroblastoma; however, in adolescents and young adults, the tumor is formed of mature ganglion cells separated by collagenous stroma and called ganglioneuroma and this is the most benign type of NBL. NBL and ganglioneuroblastoma were classified by Shimada and recently by International Neuroblastoma Pathology Classification into favorable and unfavorable histology tumors according to the degree of neuroblasts differentiation and stromal development (stroma-rich and stroma-poor) 3).

Amplification of the MYC family member, MYCN, is found in ∼25% of cases and correlates with high-risk disease and poor prognosis. Currently, amplification of MYCN remains the best-characterized genetic marker of risk in neuroblastoma. This article reviews roles for MYCN in neuroblastoma and highlights recent identification of other driver mutations. Strategies to target MYCN at the level of protein stability and transcription are also reviewed 4).

Patients with NBL may show genetic abnormalities in the form of deletion in the short arm of chromosome one and amplification of genes of chromosome two (called N myc gene amplification) and this is considered a poor prognostic factor of the disease 5).

Clinical presentation

The most common clinical presentation of abdominal NBL in children is a large flank mass; however, other rare presentations may include pelvic NBL, bilateral, pelviabdominal, and neonatal NBL, other manifestations may associate with the tumor mass-like metastatic lesions in bone or liver, pallor, abdominal pain, weight loss, and fever. NBL is a biologically active tumor secreting vanillylmandelic acid (VMA) and homovanillic acid, or other metabolites such as catecholamines, neuron-specific enolase (NSE), and vasoactive intestinal peptides in some cases 6).


NBL can be diagnosed radiologically by ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) with different sensitivities and specificities.

Three major staging systems are used for staging of NBL: Evans staging system (1971), Pediatric Oncology Group (1983) system, and the widely used International Neuroblastoma Staging System (INSS 1988).


Treatment of NBL is a multimodality therapy composed of surgery, chemotherapy, and radiotherapy either in combination or separate depending on disease stage, patient age, genetic abnormalities, tumor biology, and histological classifications 7) see esthesioneuroblastoma

Yang et al tested antitumor effects of sorafenib (≤ 10 µM) on four human neuroblastoma cell lines, CHLA255, CHLA171, CHLA90 and SK-N-AS. Sorafenib inhibited cell proliferation and induced apoptosis of neuroblastoma tumor cells in a dose-dependent manner. Sorafenib inhibited phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) proteins at Tyr705 in these cells, associated with inhibition of phosphorylated JAK2, an upstream kinase that mediates STAT3 phosphorylation. Expression of a constitutively-activated STAT3 mutant (pSTAT3-C) partially blocked the antitumor effects of sorafenib on neuroblastoma cells. Sorafenib also inhibited the phosphorylation of STAT3 induced by IL-6 and sphingosine-1-phosphate (S1P), a recently identified regulator for STAT3, in these tumor cells. Moreover, sorafenib downregulated phosphorylation of MAPK (p44/42) in neuroblastoma cells, consistent with inhibition of their upstream regulators MEK1/2 8).

Zheng T, Ménard M, Weiss WA. Neuroblastoma Metastases: Leveraging the Avian Neural Crest. Cancer Cell. 2017 Oct 9;32(4):395-397. doi: 10.1016/j.ccell.2017.09.012. PubMed PMID: 29017050.
Brodeur GM, Marris JM. Neuroblastoma. In: Pizzo, Poplack BG, editors. Principles and Practice of Pediatric Oncology. 5 th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 933-70
Shimada H, Umehara S, Monobe Y, Hachitanda Y, Nakagawa A, Goto S, et al. International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: A report from the Children's Cancer Group. Cancer 2001;92:2451-61.
Huang M, Weiss WA. Neuroblastoma and MYCN. Cold Spring Harb Perspect Med. 2013 Oct 1;3(10):a014415. doi: 10.1101/cshperspect.a014415. PubMed PMID: 24086065.
Bowman LC, Castleberry RP, Cantor A, Joshi V, Cohn SL, Smith EI, et al. Genetic staging of unresectable or metastatic neuroblastoma in infants: A pediatric oncology group study. J Natl Cancer Inst 1997;89:373-80.
Park JR, Eggert A, Caron H. Neuroblastoma: Biology, prognosis, and treatment. Hematol Oncol Clin North Am 2010;24:65-86.
Yang F, Jove V, Buettner R, Xin H, Wu J, Wang Y, Nam S, Xu Y, Ara T, DeClerck YA, Seeger R, Yu H, Jove R. Sorafenib inhibits endogenous and IL-6/S1P induced JAK2-STAT3 signaling in human neuroblastoma, associated with growth suppression and apoptosis. Cancer Biol Ther. 2012 May;13(7):534-41. doi: 10.4161/cbt.19603. Epub 2012 May 1. PubMed PMID: 22406995
neuroblastoma.txt · Last modified: 2018/05/22 23:37 by administrador