Neuroblastoma

DR. NOVI KURNIA, SPB, SUBSPPED(K)

 Neuroblastoma : why we need to know?
Most common extracranial solid tumor of childhood.
Most common intra abdominal malignancy in infancy.
8% to 10% of all childhood cancers.
>50% of the children present with metastatic disease.
up to 15% of all pediatric cancer deaths.

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
 Neuroblastoma : origin?
Neural crest  embryonal neuroendocrine tumor of the peripheral nervous system
Anywhere along the sympathetic ganglion chain from neck to pelvis, esp. the adrenal medulla

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
 Neuroblastoma: how common?
1:7.500-10.000 live birth
Male to female = 1,2:1
age at diagnosis
◦ Median 17–18 months
◦ 40% < 1 year old at diagnosis
◦ < 5% older than 10 years

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
 Neuroblastoma: unique clinical course
wide clinical heterogeneity
• spontaneous regression
• differentiation
• treatment-refractory progression despite intensive therapy.

Survival rate
◦ Low to intermediate risk disease – 85-90%
◦ High risk - < 50%

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
 Neuroblastoma:
Screening X Early diagnosis
Historical mass screening in Japan, North America and
Europe  no benefit
◦ Neuroblastoma identified by screening were most likely to
spontaneously regress

Early diagnosis  high index of suspicion

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
 Neuroblastoma: Clinical Presentation
Tumor Metastases to bony orbit orbital
ecchymosis – PANDA/RACOON EYES
General symptoms:
◦ Weight loss
◦ Failure to thrive
◦ Abdominal pain
◦ Fever
◦ Anemia
Hypertension (25%) – cathecholamine
Paraneoplastic syndrome – diarrhea
and electrolyte abnormality due to
vasoactive intestinal peptide secretion Metastases to bone  bone pain

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
 Neuroblastoma:
cathecholamine and its metabolites

Czarnecka M, Tilan J, Kitlinska J. Sympathetic Neurotransmitters in Neuroblastoma. Between Physiology and Pathology. 2012
 Neuroblastoma: Diagnosis
Imaging Lab
◦ US ◦ HMA and VMA
◦ CT scan ◦ Ferritin
◦ MRI ◦ Neuron specific enolase prognosis
◦ MIBG scintigraphy ◦ LDH
Histopathological confirmation
◦ Biopsy of lump
◦ Bone marrow biopsy

Rich BS, La Quaglia MP. Chapter 31 - Neuroblastoma. In: Coran AG, Adzick NS, Krummel TM, Laberge JM, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th ed.
Philadelphia: Mosby; 2012. p. 441-58.
Neuroblastoma: pathology
“Small round blue cell”
Subtype
◦Undifferentiated
◦Poorly differentiated
◦differentiating
 Neuroblastoma:
Staging and Risk Stratification
International Neuroblastoma Staging System  post op

Swift CC, Eklund MJ, Kraveka JM, Alazraki AL. Updates in Diagnosis, Management, and Treatment of Neuroblastoma. Pediatric Imaging. 2018.
 Neuroblastoma:
Staging and Risk Stratification
International Neuroblastoma Risk Group Staging System  pre op

Swift CC, Eklund MJ, Kraveka JM, Alazraki AL. Updates in Diagnosis, Management, and Treatment of Neuroblastoma. Pediatric Imaging. 2018.
 Neuroblastoma:
Staging and Risk Stratification
Image Defined Risk Factor

Swift CC, Eklund MJ, Kraveka JM, Alazraki AL. Updates in Diagnosis, Management, and Treatment of Neuroblastoma. Pediatric Imaging. 2018.
Neuroblastoma:
Risk Stratification
 Neuroblastoma:
Risk Stratification
international neuroblastoma pathology classification

Nakazawa A. Biological categories of neuroblastoma based on the international neuroblastoma pathology classification for treatment stratification. Pathology
International. 2021; 71(4): 232-244.
Neuroblastoma: Management
Determine risk group
 low-, intermediate-, or high-risk group

◦INSS/INRGSS stage
◦age at diagnosis
◦the histologic results
◦the biology and genetics of the tumor
Children’s Oncology Group
Neuroblastoma Risk Group
International Neuroblastoma Risk Group (INRG)
classification system
Neuroblastoma: management modalities
Surgery
Chemotherapy
Radiotherapy

Immunotherapy
I-131 MIBG therapy
Neuroblastoma: management
Very Low Low
observation Surgery
Short course chemotx for
symptomatic cord
compression or respiratory
problem
Stage 4S: supportive care or
short course chemotx
Intermediate High
Primary resection Induction chemotx
Standard chemotx Surgical resection
Consolidation therapy –
Neoadjuvant chemotx for myeloablative chemotx with
initially unresectable stem cell rescue and radiotx to
tumor bed
Maintenance tx
Chemotherapy
1st line Stage IV response
◦ Unresponsive 30%
◦ Cyclophosphamide ◦ Partial response 30%
◦ Complete response 40%
◦ Vincristine
◦ Dacarbazine

2nd line
◦ Doxorubicin
◦ Teniposide
Immunotherapy
13-cis-retinoid acid
◦ In vitro  down-regulate N-myc mRNA expression, which arrests tumor cell
proliferation.
◦ Improved survival in patients with minimal disease
antibody targeting neuroblastoma tumor antigen GD2
◦ dinutuximab and naxitamab in combination with granulocyte-macrophage
colony-stimulating factor (GM-CSF), interleukin-2 (IL-2)
◦ Improve both event-free survival and overall survival
Myeloablative therapy
Melphalan, Doxorubicin, Teniposide, and low-dose total-
body irradiation
Followed by autologous bone marrow transplant
MIBG therapy
I-131
Stage III or IV with MIBG avid lesion at diagnostic
MIBG scintigraphy
Conclusion
Highly variable clinical course
Risk stratification is important
Poor outcome in high risk group