184 53

Hellenic Journal of Surgery 2010; 82: 2

Neuroblastoma in Childhood

Review Article

Μ. Filippou, Α. Vassiliou, G. Sakellaris

Received 30/10/2009 Accepted 18/03/2010

Abstract paediatric cancer overall. The incidence of NB is

A small but significant percentage of patients that 1/100,000 children. More than 50% of patients are
Neuroblastomas (NB) are the most common solid older than two years of age at diagnosis, and more
tumour in children under the age of five. The aeti- than 70% are under the age of five [3]. With a ra-
ology remains unknown, although it has been asso- tio of 1.2:1.0, there is a preponderance of boys over
ciated with several genes, such as MYCN in chro- girls who have the disease [4]. Mothers of children
mosome 17q and LOH in chromosome 1q. The with NB have been described to have displayed red-
incidence of the disease is 1/100,000 children. Clini- ness and hypertension during pregnancy. This is
cal signs and symptoms vary according to the age of very important for perinatal guidance [4].
patient, the stage of NB, metastases and the secre- As NBs are neuro-ectodermal tumours of embry-
tion of several metabolic products by the tumour. onic neural crest-derived cells, a primary NB le-
Ninety per cent of NB produces catecholamines. sion is usually found somewhere along the sym-
Diagnosis is usually based on characteristic histo- pathetic axis, most commonly in an adrenal gland.
logical findings. According to the Children’s Study [4,5]. The neural crest in normal development gives
Group (CSG) and the International Neuroblastoma rise to nerve cells of the sympathetic nervous sys-
Staging System (INSS) NB has four stages. The tem (SNS). This is formed by the sympathetic side
therapeutic approach is based on the stage of the chains and sympathetic ganglia, which run along-
disease, while age, stage of disease, histological and side the ventral side of the spine, and the adrenal
biological markers are used to predict prognosis. In medulla. Since NB can arise from any site along the
conclusion, given that correct treatment and prog- sympathetic nervous system chain, the locations of
nosis depend mainly on the stage of NB, we urge primary tumours at the time of diagnosis are varied
great care in the staging of the disease. and change with age (Table 1). The foetal adrenal
medulla consists of a mixture of chromaffin cells
Keywords and clusters of mature ganglion cells. Chromaffin
Neuroblastoma, Neural crest, Catecholamine, MYCN, LOH cells are neuro-endocrine in origin and produce the
stress hormones norepinephrin and epinephrine.
Introduction Ganglion cells are interconnecting nerve cells be-
The past decades have witnessed significant ad- tween pre- and postganglionic sympathetic nerve
vances in children’s cancer therapy that have led to fibres. The adrenal medulla strongly increases the
the currently more encouraging survival figures for amount of chromaffin cells after birth, in concert
low- and intermediate-risk neuroblastomas. None- with a gradual loss of ganglion cells. ΝΒs most likely
theless, the overall survival for high-risk neuroblas- originate from both cells types or from a pluripotent
toma remains below 50%[1,2]. precursor cell, since they can contain cells with neu-
The term Neuroblastoma is commonly used to re- ral and chromaffin cell properties [6].
fer to a spectrum of neuro blastic tumours that in- The aetiology of the disease remains unknown.
clude neuroblastomas, ganglioneuroblastomas and It has been found that several genes associate with
ganglioneuromas [3]. Neuroblastomas (NB) are NB, such as MYCN in chromosome 17q and LOH
the most common solid tumour in children under in chromosome 1q [6]. The tumour usually has a
the age of five and ranks as the third most common multiple clinical presentation related to the pa-
tient’s age, stage of disease, metastases and the se-
cretion of several specific metabolic products by the
tumour [10]. Metastasis spreads to the bone, bone
Department of Paediatric Surgery, University General Hospital marrow or liver, with occasional pulmonary or brain
of Heraklion, Crete, Greece
involvement, the latter more commonly
e-mail: [email protected]
54 185
Neuroblastoma in Childhood Hellenic Journal of Surgery 2010; 82: 2

Table 1 Primary Sites of Neuroblastoma According to Age Stage ΙΙΙ: usually refers to a large tumour, extending
beyond the midline and often unresectable, leaving
Site ≤ 1 Year (%) > 1 Year gross residual disease. It has spread to contralateral
or bilateral lumph nodes.
Cervical 4 0.5
Stage IV: disease involves distant metastases to the
Thoracic 29 14 skeletal tissues, other organ soft tissues, or distant
Abdominal lymph nodes.
Adrenal 25 40 Stage ΙV-S: children under the age of 1 year with
Nonadrenal 26 32
metastases confined to liver, skin or bone marrow,
without evidence of metastases.
Pelvic 3 2.5
Over a period of forty years, a data collection from
Other 13 9
Europe and USA allowed a classification of the pa-
Unknown 0 2 tients into risk categories. This classification strati-
fies patients based on the risk of NB progression
and mortality and emphasizes a multidisciplinary
approach to treatment [4].
at relapse. Metastases can also occur in utero. Out-
come is heavily associated with age at diagnosis and Risk Groups for Treatment
certain biologic features [5,10]. The International Neuroblastoma Classification
The International Neuroblastoma Pathology Clas- scheme is used in conjunction with the Internation-
sification (INPC) has standardized the reporting al Neuroblastoma Staging System (INSS) (Table 2),
and prognostic evaluation of the histological fea- age, ploidy and MYCN status for the determination
tures of NB. The classification quantifies the degree of risk category, according to the Children’s Oncol-
of cellular differentiation, atypia, mitosis and death. ogy Group (COG), for the purpose of treatment
[1] Neuroblastoma is distinguished from gaglioneu- selection. Patients are classified into low-, interme-
roma by stroma-poor appearance. The neuroblastic diate- and high- risk categories based upon the fol-
cells form nests of cells known as Horner Wright lowing characteristics (Table 3) [3,10]:
rosettes. The differentiation of Neuroblastoma is • Stage of the disease at first diagnosis
defined based on the proportion of cells exhibiting • Patient age
morphological features of developing ganglion cells. • Histologic appearance of the tumour
The undifferentiated NB cells are small; they have • Quantitative DNA content of the tumour
a thin or indiscernible rim of cytoplasm, hyperchro- (DNA index or ploidy)
matic nuclei with distinct nucleoli and lack neuropil • Presence or absence of amplification of the
(thin neuritic processes). The increasing frequency MYCN oncogene
of neuroblasts resembling differentiating ganglion
cells and the presence of neuropil are associated Current Treatment
with increasingly differentiated neuroblastomas [3]. Low-Risk Group
According to the Children’s Study Group and the In- Patients in the low-risk category generally have low
ternational Neuroblastoma Staging System (INSS), stage disease and favourable MYCN status, DNA
neuroblastoma has four stages [3]: ploidy and histology. Low- risk patients are primar-
Stage Ι: refers to a tumour confined to a single or- ily treated with observation (stage ΙV – S) or sur-
gan or structure that can be completely resected [8] gery (stage Ι and ΙΙ).
and does not cross the midline. Microscopic residual The goal of surgery is to establish the diagnosis of
disease may be present. Non-adherent lymph nodes NB and to extirpate stage I and II tumours. Resect-
may not contain a tumour, but resected adherent ability is determined by tumour location and mobil-
nodes may contain metastases. ity, relationship to major nerves and blood vessels,
Stage ΙΙ: indicates a tumour that extends beyond the presence of distant metastases and age of pa-
the organ of origin but does not cross the midline. tient. Sacrifice of vital organs to achieve a complete
Local lymph nodes can be involved [8]. Stage IIA resection of large primary tumours at the time of
indicates disease with an incompletely resected lo- diagnosis should be avoided, particularly in infants
calized tumour without spread to non-adherent ipsi- who have a favourable prognosis. In such patients,
lateral lymph nodes. Stage IIB describes a localized surgery should be delayed and combination che-
tumour with spread to ipsilateral but not contralat- motherapy administered to reduce the size of the
eral lymph nodes. tumour.
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Hellenic Journal of Surgery 2010; 82: 2 Neuroblastoma in Childhood

Table 2 International Neuroblastoma Staging System (INSS) study reported a five-year EFS and overall survival
[3,10, 22, 23, 24] rates with surgery alone of 81% and 98%, respec-
Stage Organ Midline Microscopic Non-Adherent tively [11]. Only 7 of the 23 patients with incom-
Disease Lymph Nodes pletely resected disease developed recurrent dis-
I Single Organ Not Crossed May be Present No ease, and all were successfully salvaged with further
IIA Beyond the
surgery or multimodality chemotherapy.
Organ of Origin Not Crossed Present No
IIB Beyond the
Chemotherapy is reserved for symptomatic pa-
Organ of Origin Not Crossed Present Ipsilateral tients with spinal cord compression and stage IV-S
III Large Tumour Crossed Present Contralateral patients with respiratory compromise secondary to
or Bilateral hepatic infiltration. The treatment comprises low
IV Large Tumour, Crossed Present Distant
dose carboplatin, cyclophoshamide, cisplatin, doxo-
Metastasis to
Other Organs
rubicin and etoposide or teniposide for 6-12 weeks,
IV-S Children under the age of 1 year with resectable primary tumour in order to minimize the long-term deleterious ef-
and metastases confined to liver, skin or bone marrow. fects of regimen. Children with asymptomatic stage
IV-S NB receiving supportive care only may expect
Table 3 International Neuroblastoma Staging System (INSS) 100% survival. While still investigational, stage
[3,10, 22, 23, 24] I adrenal Neuroblastoma without involvement
INSS Age MYCN Shimada DNA Risk of the spinal canal diagnosed perinatally may be
Stage Status Histology Ploidy Group monitored without resection or chemotherapy [3].
Ι 0-21 Any Any Any Low
Among patients who have favourable localized but
ΙΙΑ/ <1 Any Any Any Low
ΙΙΒ
unresectable disease, primary chemotherapy may
>1 NonAmp Any - Low be used to shrink the primary tumour and resection
>1 Amp Favourable - Low delayed until it can be performed safely [19-21].
>1 Amp Unfavourable - High Radiation therapy (RT) is reserved for unresect-
ΙΙΙ <1 NonAmp Any Any Intermediate
able tumours or progressive tumours unresponsive
<1 Amp Any Any High
>1 NonAmp Any - Intermediate
to chemotherapy [10].
>1 NonAmp Unfavourable - High A high rate of spontaneous regression is seen
>1 Amp Any - High in infants with stage IV-S disease; as a result, treat-
IV <1 NonAmp Any Any Intermediate ment can be deferred in some cases [22,25]. Al-
<1 Amp Any Any High
though survival is excellent with minimal or no
>1 Any Any - High
ΙV – S <1 NonAmp Favourable >1 Low
therapy, subsets of patients with IV-S disease and a
<1 NonAmp Any =1 Intermediate poor prognosis can be identified by risk factors such
<1 NonAmp Unfavourable Any Intermediate as an age of less than two months and MYCN am-
<1 Amp Any Any High plification [22].
NMYC status: Amp (amplified) NonAmp (non amplified) In one report of 80 infants with IV-S disease, none
DNA Ploidy: DNA INDEX (DI) =1 unfavourable >1 favourable of whom had MYCN amplification, the five-year
EFS and overall survival rates were 86% and 92%,
Two- to five-year event-free survival (EFS) rates in respectively [25]. All 44 infants who received sup-
excess of 95% have been recorded for surgery alone portive care alone were alive at five years, compared
in children with stage 1 disease; since recurrences to 81% of those who required cytotoxic therapy for
can be successfully managed with further surgery or symptoms. Five of the six deaths were in infants
chemotherapy, five-year survival rates reach 99% younger than two months of age and were due to
[11-14]. extensive abdominal involvement, suggesting that
For children with stage IIA or IIB disease, the out- aggressive initial therapy should be considered in
look is somewhat less predictable, but still relatively these patients.
favourable. Historically, many of these patients re- Based upon this experience with infants with 4S
ceived chemotherapy and their survival was excel- disease, the same strategy of initial observation has
lent [15,16]. Increasingly, these patients are man- been applied to children less than one year of age
aged with surgery alone. Several single-institution with localized neuroblastoma (stage I, II, or III)
and cooperative-group studies have shown that the without MYCN amplification. In a prospective,
elimination of chemotherapy has no detrimental nonrandomized multicenter study, 93 of 340 chil-
impact on survival and only about 20% of patients dren (27 %) were observed without either primary
will require further therapy [11,14,17,18]. By way of resection of gross residual tumour or chemotherapy
illustration, one Children’s Cancer Group (CCG) following the initial diagnosis [26].
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Neuroblastoma in Childhood Hellenic Journal of Surgery 2010; 82: 2

Intermediate-risk Group ease but with either positive lymph nodes or residu-
Intermediate-risk patients are treated with sur- al tumour after initial surgery [36]. Currently, most
gery and 12-24 weeks of chemotherapy, using the cooperative groups withhold RT for the majority of
same regimen as for the low-risk group. The role patients with intermediate-risk disease, and recom-
of surgery is to establish the diagnosis at presenta- mend it only in the setting of disease progression
tion. Following chemotherapy, surgical resection is despite surgery and chemotherapy, or for patients
recommended. Achieving complete gross or even who have primary tumours with unfavourable bio-
partial resection correlates with improved survival logic features that remain unresectable after induc-
compared to biopsy alone. However, sacrificing adja- tion chemotherapy.
cent structures is not recommended since survival of
patients undergoing complete and partial resection is High-risk Group
equivalent. At 3 years, 70-90% survival is expected Historically, the long-term survival probability for
for children in the intermediate-risk group [3]. children with high-risk disease was less than 15%.
Surgery is an important component of treatment Better results have been achieved using an aggres-
for children with intermediate-risk neuroblastoma, sive multimodality approach that includes chemo-
but is inadequate by itself [27,28]. Furthermore, for therapy, surgical resection, high-dose chemotherapy
children with widespread disease, complete resec- with hematopoietic stem-cell rescue, and radiation
tion may not be possible initially because of proxim- therapy [3,10,37,38]. However, current survival
ity to vital structures. The importance of gross total rates remain unacceptably low (approximately
resection in patients with disseminated disease is 30%), and the improved outcome has come at the
controversial, with most reports [29,30,33], but not cost of significant early and late toxicity.
all [28,34], suggesting a better outcome for complete Treatment regiments consist of three phases (in-
resection. duction, consolidation and maintenance) reminis-
Moderately intensive multiagent chemotherapy cent of the successful strategy employed against
(eg, with doxorubicin, cyclophosphamide, a plati- acute lymphoblastic leukemia [37].
num drug, and etoposide) is recommended for chil- The goal of the induction phase is the removal of
dren with intermediate-risk neuroblastoma and is gross tumour and achievement of local control. In-
often applied before attempted resection [29]. The tensive chemotherapy with a combination of agents,
success of a combined-modality approach to treat- including platinum agents, cyclophosphamide, doxo-
ment was illustrated in a report from the CCG, in rubicin and etoposide, is used to shrink primary and
which 143 children met the criteria for intermediate- metastatic tumours; teniposide may be used outside
stage disease according to the COG risk assessment of the United States [39]. Surgical removal of gross
schema [29]. Patients received five courses of che- residual disease and radiotherapy to the primary
motherapy over a period of 15 weeks, followed by tumour are required for adequate local tumour
surgery, one more course of chemotherapy, RT for control. Surgical resection of the tumour is critical
gross residual disease, and 16 additional weeks of to outcome and should be performed by a paediat-
chemotherapy. The four-year EFS and overall sur- ric surgeon with experience in resecting extensive,
vival rates for patients with normal MYCN and fa- infiltrating tumours. Resection may be performed
vourable histology was 100% each, while for infants after an initial course of chemotherapy when the
with at least one unfavourable biologic feature, they tumour is smaller and less invasive. Radiotherapy
were 90% and 93%, respectively. In contrast, for (24 to 30 Gy) dosed to the primary tumour bed and
older children with unfavourable features, the EFS other sites of bulky disease may be beneficial in pre-
and overall survival rates were only 54% and 65%, venting local tumour recurrence [40-43].
respectively. After tumour bulk has been decreased by che-
The role of RT for patients with locoregional dis- motherapy and surgery, the consolidation phase
ease is unclear. In a randomized study conducted includes higher-dose chemotherapy followed by au-
by the Paediatric Oncology Group (POG) in 62 pa- tologous hematopoietic stem cell rescue [37,38,44].
tients with INSS stage 2B and 3 disease, the addition The fact that the majority of high-risk patients have
of RT (24 to 30 Gy) to the tumour bed and regional bone marrow metastases at the time of diagnosis
nodes following chemotherapy significantly im- would appear to compromise the use of autologous
proved two-year disease-free survival (59% versus marrow for reconstitution. The CCG “purged” the
32%) and significantly improved survival. In con- stem cells of tumour using an immunomagnetic ap-
trast [35], a lack of benefit was reported in a second proach [37].
trial involving 29 patients with non-metastatic dis- The final component of therapy is geared toward
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Hellenic Journal of Surgery 2010; 82: 2 Neuroblastoma in Childhood

eradication of minimal residual disease through bio- specific antigens using passive antibody transfer
logic differentiation therapy with cis-retinoic acid or priming of host T cells. [51,52] . Further stud-
[37]. This agent was first demonstrated to induce ies are investigating the use of immunocytok-
the differentiation of neuroblastoma cells in vitro ines, or tumour-specific antibodies genetically
[45,46]. The CCG3891 randomized clinical trial linked to a cytokine to enhance the local immu-
demonstrated cis-retinoic acid to be the first effec- nologic effect [53]. An alternative immunologic
tive biologic therapeutic agent for treatment of high- approach under investigation is the engineer-
risk neuroblastoma, improving the recurrence risk ing of tumour-specific cytotoxic T lymphocytes
for patients regardless of whether they had received (CTL). Previous attempts at infusing effector T
myeloablative or conventional chemotherapy [44]. cells expressing a chimeric receptor recognizing
Despite intensive multimodality therapy, only GD2 have failed due to poor in vivo survival,
approximately 30% of children remain disease- despite supplementation with exogenous growth
free long-term, and the most common outcome of factors and ex vivo stimulation. Similar toler-
high-risk neuroblastoma is recurrence of disease fol- ability with lack of in vivo T-cells survival has
lowed by death [43]. Pilot studies of even more in- also been demonstrated with T-cells expressing
tensive therapy over a longer duration of time, such alternative anti-neuroblastoma directed recep-
as tandem transplants (ie, more than one course of tors [54].
high-dose therapy with autologous stem cell rescue
in rapid succession) show some promise, with re- B. Targeted Radiotherapy
ports suggesting survival rates of over 50% for up to Approximately 90% of neuroblastomas actively
seven years [47-50]. uptake radiolabelled metaiodobenzylguanidine
(MIBG), a norepinephrine analogue internal-
Recurrent Neuroblastoma ized by adrenergic tissue. Use of the 131I-la-
Recurrent NB is treated based on initial risk stratifi- beled-MIBG isotope is one strategy for targeted
cation, patient age, extent of recurrent disease, and radiotherapy against neuroblastic tumours [55].
tumour biology at the time of recurrence. Local and
regional recurrences in children initially classified as C. Targeted Biologic Therapies
low-risk are resected with the expectation of long- i. Retinoids
term survival. If complete resection is not feasible The retinoids are naturally occurring vitamin
or a recurrent tumour has favourable biological A analogues involved in a variety of cellu-
characteristics, 12-24 weeks of chemotherapy are lar processes, including neuronal develop-
added. Older children with an unfavourable his- ment and differentiation [56]. Integration of
tology or NMYC amplification require aggressive cis-retinoic acid into neuroblastoma mainte-
chemotherapy and possibly myeloablative therapy nance therapy has resulted in an incremental
and stem cell transplantation. Recurrent disease increase in event-free survival rate [37,44].
in children, initially classified as intermediate-risk, Further study of this family of molecules has
is treated with surgery followed by chemotherapy. yielded fenretinide, a synthetic retinoid. This
NB progression, recurrence or metastases, occur- compound has demonstrated efficacy in a
ring during chemotherapy or within 3 months of number of animal cancer models, including
treatment are associated with a poor prognosis, neuroblastoma [57].
and require aggressive regimens using multidrug ii. Neurotrophin Inhibitor
chemotherapy, myloablative therapy and stem cell Several studies in vitro have demonstrated the
transplantation. Recurrent NB in high-risk patients aberrant expression of Trk family members in
carries a poor prognosis [3]. neuroblastomas. These receptors are responsi-
ble for transmitting extracellular signals from
Novel Therapies nerve growth factors, including brain-derived
A myriad of novel therapeutic approaches have neutrophic factor (BDNF), nerve growth fac-
been investigated over the past several years. Con- tor (NGF) and neutrophin-3(NT-3) [58]. They
ventional chemotherapeutics are nearing their max- are consequently important players in nerve
imum potential with regards to efficacy and patient cell development and maintenance. Increased
tolerance. expression of TrkB, the receptor for BDNF,
A. Targeted Immunotherapy has been associated with high-risk neuroblas-
Immunologic approaches to neuroblastoma toma, while elevated Trk A and Trk C are ob-
therapy thus far have included targeting tumour- served in more favourable disease [59].
58 189
Neuroblastoma in Childhood Hellenic Journal of Surgery 2010; 82: 2

iii. ALK Inhibitor Models, 2006;4(3):387-390

The anaplastic lymphoma kinase (ALK) is a 5. Cohn SL, Pearson AD, London WB et al, The International
Neuroblastoma Risk Group (INRG) classificationsystem: an
receptor tyrosine kinase whose gene is mu- INRG Task Force report, J Cl Oncol, 2009;27:289-297
tated or rearranged in a large proportion of 6. Noesel MM, Versteeg R, Pediatric neuroblastomas: genetic
lymphoblastic and anaplastic large cell lym- and epigenetic “Danse Macabre”, Gene 325, 2004: 1-15
phomas and some non-small cell lung cancers. 7. Schwab M, Westermann F, Hero B et al, Neuroblastoma: bi-
ology and molecular and chromosomal pathology, The Lancet
Signalling though this pathway, while incom- Oncology, 2003;8(4):472-480
pletely characterized, appears to be important 8. Ross RA, Spengler BA, Human neuroblastoma stem cells,
for neuronal differentiation [60]. A recent sig- Seminars in Cancer Biology, 2007;3(17): 241-247
nificant finding was the identification of germ 9. Raffaghelllo L, Pistoia V, Immunotherapy of neuroblasto-
ma: present, past and future, Expert Rev. Neurotherapeutics,
line ALK mutations in several familial neuro-
2006;6(4):509-518
blastoma cohorts [61]. Further investigation
10. KJ Welch, JG Randolph, MM Ravitch, JA O’ Neil, Jr, MI
has identified several novel ALK mutations Rowe, Pediatric Surgery, Fourth Edition, p. 282-293
in both primary neuroblastoma tumours and 11. Perez CA, Matthay KK, Atkinson JB et al, Biologic variables
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13. Kusher BH, Cheung NK, LaQuaglia MP et al, International
neuroblastoma staging system stage 1 neuroblastoma: a prospec-
Conclusions tive study and literature review, J Clin Oncol, 1996;14:2174
NB is a very rare disease. However, we need to be 14. Evans AE, Silber JH, Shpilsky A et al, Successful manage-
alert since it is the most common solid tumour in ment of low-stage neuroblastoma without adjuvant therapies: a
comparison of two decades, 1972 through 1981 and 1982 through
childhood and although in very early stages it has a
1992, in a single institution, J Clin Oncol, 1996;14:2504
better prognosis, it usually escapes diagnosis. As soon 15. Bowman LC, Castleberry RP, Cantor A et al, Genetic staging
as the diagnosis is confirmed, staging of the tumour of unresectable or metastatic neuroblastoma in infants: a Pediat-
must be done and the patients be assigned to low- ric Oncology Group study, J Natl Cancer Inst, 1997;89:373
16. Castleberry RP, Shuster JJ, Altshuler G et al, Infants with
risk, intermediate-risk or high-risk-group.
neuroblastoma and regional lymph node metastases have a fa-
In the case of large tumours, it is better to initiate vourable outlook after limited postoperative chemotherapy: a
treatment with chemotherapy and subsequently pro- Pediatric Oncology Group study, J Clin Oncol, 1992; 10:1299
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cation is a major prognostic factor in localized neuroblastoma:
Patients that survive still carry a risk of recurrence,
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chemotherapy, radiation therapy and stem cell primary chemotherapy, BR J Cancer, 2003;89:1605
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morbidity has not decreased. Further research into
21. Leclair MD, Hartmann O, Heloury Y et al, Localized pelvic
immunotherapy and genetic treatment is manda- neuroblastoma: excellent survival and low morbidity with tai-
tory. lored therapy – the 10th year experience of the French society of
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22. Katzenstein HM, Bowman LC, Brodeur GM et al, Prognos-
Conflict of interest tic significance of age, MYCN oncogene amplification, tumor
The authors declare that they have no conflict of cell ploidy and histology in 110 infants with stage IV-S neuro-
interest. blastoma: a pediatric oncology group experience, J Clin Oncol,
1998;16:2007
23. D’Angio GJ, Evans AE, Koop CE, Special pattern of wide-
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Neuroblastoma in Childhood Hellenic Journal of Surgery 2010; 82: 2

Νευροβλάστωμα της Παιδικής Ηλικίας

Άρθρο Ανασκόπησης

Μ. Φιλίππου, Α. Βασιλείου, Γ. Σακελλάρης

Περίληψη
Ένας από τους πιο συχνούς συμπαγείς όγκους στα
παιδιά κάτω των 5 ετών είναι το νευροβλάστωμα
(ΝΒ). Η αιτιολογία του παραμένει άγνωστη αν
και έχουν ενοχοποιηθεί γονίδια, όπως είναι το
MYCN του χρωμοσώματος 17q και το LOH του
χρωμοσώματος 1q. Η επίπτωση της νόσου είναι
1/100.000 παιδιά. Η κλινική εκδήλωση του όγκου
κυμαίνεται ανάλογα με την ηλικία του ασθενούς
και το στάδιο της νόσου. Συνήθως έχει πολλαπλή
κλινική εκδήλωση η οποία σχετίζεται με τον όγκο,
τη μετάσταση και την παραγωγή συγκεκριμένων
μεταβολικών προϊόντων του όγκου. Τα 90% των
παιδιών παράγουν κατεχολαμίνες. Η διάγνωση
του ΝΒ συνήθως βασίζεται στα χαρακτηριστικά
ιστολογικά ευρήματα. Όμως ο ιστολογικός τύπος
της νόσου ποικίλει. Μεταστάσεις παρατηρούνται
λόγω αιματογενούς, λεμφογενούς και κατά
συνέχεια ιστού μεταφοράς παθολογικών κυττάρων.
Σύμφωνα με το Children’s Study Group (CSG)
και το International Neuroblastoma Staging Sys-
tem (INSS) έχουμε 4 στάδια στο νευροβλάστωμα.
Η θεραπευτική προσέγγιση της νόσου γίνεται
με βάση το στάδιο του όγκου. Η πρόγνωση του
ΝΒ εξαρτάται από την ηλικία του ασθενούς, το
στάδιο της νόσου και την εντόπιση του αρχικού
όγκου. Συμπερασματικά είναι πολύ σημαντικό να
κατατάσσονται οι ασθενείς στο σωστό στάδιο
της νόσου έτσι ώστε οι υψηλού κινδύνου ασθενείς
να έχουν επιθετική θεραπέια και οι χαμηλού και
μεσαίου κινδύνου να θεραπεύονται με ήπια μέσα για
να μπορέσουμε έτσι στη μείωση της θνητότητας.

Λέξεις κλειδιά: Νευροβλάστωμα, Νευρική ακρολοφία,

Κατεχολαμίνες, MYCN, LOH

Κλινική Χειρουργικής Παίδων, Πανεπιστημιακό Νοσοκομείο Ηρακλείου