Neuroblastoma Flashcards
Pediatric Maligancies
BONUS:
What is the most common extracranial tumor of childhood?
Neuroblastoma
Neuroblastoma
Infant screening led to a decrease in the mortality rates when compared to non-screened control population.
TRUE or FALSE?
True
Neuroblastoma
What urinary metabolites can be quantitatively assayed by HPLC and normalized to urinary creatinine to detect for neuroblastoma?
homovanillic acid (HVA) vanillylmandelicacid (VMA)
Neuroblastoma
What urinary metabolite of epinephrine can be qualitatively to detect for neuroblastoma?
vanillylmandelicacid (VMA)
Neuroblastoma
NB may arise from any site in the sympathetic nervous system.
What are the most common sites of origin?
adrenal medulla (30-40%)
paraspinal ganglia in the abdomen or pelvis (25%)
thoracic (15%)
head and neck (5%)
Neuroblastoma
What are the most common sites of metastases?
lymph nodes,
bone
bone marrow
skin
(lung and cns are rare sites)
Neuroblastoma
NB may spontaneously regress to a mature ______?
ganglioneuroma
Neuroblastoma
What is the most common presenting symptom?
pain
Neuroblastoma
What “sign” is the term used to describe the skin metastases due to its tinge?
blueberry muffin sign
Neuroblastoma
What syndrome is an unusual presentation of localized NB that is manifested by truncal ataxia and cerebellar encephalopathy, which indicates a favorable prognosis but may have lasting neurologic sequelae after successful therapy?
opsoclonus–myoclonus syndrome
Neuroblastoma
I. Pathologic evaluation of bone marrow is also a requirement for
staging of neuroblastoma.
II. Characteristically, neuroblastoma in bone marrow
appears in clumps and pseudorosettes.
III. The absence of pseudorosettes
eliminates the possibility of neuroblastoma.
I and II are true?
II and III are true?
only II is true?
all are true?
I and II only.
Neuroblastoma
A ratio of VMA to HVA >1.5 is associated with an unfavorable prognosis in patients with metastatic neuroblastoma.
TRUE or FALSE?
False.
Favorable.
Neuroblastoma
Poor scintigraphic response on __________(nuclear scan procedure) after induction chemotherapy has
been shown to predict for a poor event-free survival in patients undergoing high-dose
chemotherapy with stem cell rescue.
123I-MIBG scans
Neuroblastoma
The expression of somatostatin receptors by neuroblastoma tissues is a favorable
prognostic factor
TRUE or FALSE?
True.
Like other neural crest–derived
neoplasms, neuroblastoma can express somatostatin receptors.
The long-acting
somatostatin analog octreotide labeled with 123I has been used to image
neuroblastoma with a sensitivity comparable to that of 131I-MIBG.
The
expression of somatostatin receptors by neuroblastoma tissues is a favorable
prognostic factor
Neuroblastoma
In imaging/staging of NB, what modality often overstages stage I tumors?
MRI
Neuroblastoma
In imaging/staging of NB, what modality often understage stage II tumors?
CT
Neuroblastoma
The most commonly used staging system is the International Neuroblastoma Staging System.
This system was established to stage patients before any treatment and is based on clinical criterial and image-defined risk factors.
TRUE or FALSE?
False.
The INSS uses clinical, radiographic, and surgical findings.
(INRG is the one described in the question)
Neuroblastoma
Identify the INSS stage:
Localized tumor with incomplete gross excision;
representative ipsilateral nonadherent lymph nodes negative for tumor microscopically
INSS Stage 2A
Neuroblastoma
Identify the INSS stage:
Localized tumor with complete gross excision, without microscopic residual disease;
representative ipsilateral lymph nodes negative for tumor microscopically
(nodes attached to and removed with the primary tumor may be positive)
INSS Stage 1
Neuroblastoma
Identify the INSS stage:
Localized tumor with or without complete gross excision, with
ipsilateral nonadherent lymph nodes positive for tumor;
enlarged contralateral lymph
nodes must be negative microscopically
INSS Stage 2B
Neuroblastoma
Identify the INSS stage:
Unresectable unilateral tumor infiltrating across the midline,
with or without regional lymph node involvement;
or localized unilateral tumor with contralateral regional lymph node involvement;
or midline tumor with bilateral
extension by infiltration (unresectable) or by lymph node involvement
INSS Stage 3
Neuroblastoma
Identify the INSS stage:
Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs
INSS Stage 4 or 4S
Neuroblastoma
Identify the INSS stage:
Localized primary tumor as defined for stage 1, 2A, or 2B with dissemination limited to skin, liver, and/or bone marrow (limited to infants <1 year of age)
INSS Stage 4S
Neuroblastoma
Identify the INRG stage:
Metastatic disease in children younger than 18 months with metastasis confined to the skin, liver, and/or bone marrow
INRG Stage MS
Neuroblastoma
Identify the INRG stage:
Distant metastatic disease
INRG Stage M or MS
Neuroblastoma
Identify the INRG stage:
Locoregional tumor with
presence of one or more image-defined factors
INRG Stage L2
Neuroblastoma
Identify the INRG stage:
Localized tumor not involving
vital structures as defined by the list of image-defined risk factors and confined to one body compartment
INRG Stage L1
Neuroblastoma
Bonus:
Identify the Evans and D’Angio stage:
Tumor extending in continuity
beyond the midline; regional lymph nodes may beinvolved bilaterally.
Stage III
Evans and D’Angio stages range from I to IV and IV-S
Neuroblastoma
Bonus:
Identify the POG stage:
Complete or incomplete resection of primary, intracavitary nodes not adhered to primary histologically positive for tumor; liver histologically free of tumor
POG Stage C
POG stages range from A to D and DS
Neuroblastoma
In the INSS staging, what is meant by “minimal” involvement of marrow?
<10% of total nucleated cells
identified as malignant on bone marrow biopsy or on marrow aspirate
or negative MIBG if performed
Neuroblastoma
What are the three tumor types representing different degrees of differentiation?
Ganglioneuroma (most mature)
Ganglioneuroblastoma
Neuroblastoma
Neuroblastoma
IHC staining characteristics of NB?
positive for:
- neurofilaments
- neuron-specific enolase (NSE)
- synaptophysin
- chromogranin A
negative for:
- muscle
- leukocyte antigens
Neuroblastoma
What three histologic features along with the patient’s age at diagnosis divide the patients into favorable and unfavorable prognostic groups (Shimada classification)
stromal development (poor or rich)
neuroblastic differentiation
mitosis–karyorrhexis index of neuroblastic cells.
Neuroblastoma
What are the two most important factors that influence outcome in neuroblastoma
age and stage at initial presentation
Neuroblastoma
What gene amplification has been associated with the multidrug resistance gene, which may account for this tumor’s notorious resistance to therapy?
Allelic loss of the arm on which it resides is also associated with poor prognosis independent of age and stage.
MYCN (N-myc) on the short arm of chromosome 2.
Neuroblastoma
What mutations have also been described in neuroblastoma and have been
identified as the predisposition gene for familial neuroblastoma?
Mutations in ALK (encoding anaplastic lymphoma kinase)
Neuroblastoma
Ferritin levels considered unfavorable?
> 143 ng/mL
Neuroblastoma
Neuron-specific enolase levels considered unfavorable?
> 100
Neuroblastoma
Chromogranin levels considered unfavorable?
> 190 ng/mL
Neuroblastoma
GD2 ganglioside levels considered favorable? unfavorable?
f: <103 pmol/mL
u: >568 pmol/mL
Neuroblastoma
DNA index considered unfavorable?
1
>1.1 is considered favorable
Neuroblastoma
For low-stage, resectable tumors (INSS 1-3 with negative nodes), gross resection alone confers an excellent prognosis. adjuvant treatment has not improved outcomes for completely resected tumors with favorable prognosis.
TRUE or FALSE?
True
Neuroblastoma
Re: low-stage, resectable tumors (INSS 1-3 with negative nodes), favorable group.
ALL positive surgical margins or microscopic residual require more aggressive therapy.
TRUE or FALSE?
False
Positive
surgical margins or microscopic residual disease does not uniformly require
more aggressive therapy.
Neuroblastoma
Re: low-risk disease
What subgroups may require adjuvant therapy?
those with N-myc amplification or low DNA index
Neuroblastoma
What is the treatment for intermediate-risk patients with intraspinal extension of neuroblastoma and have severe neurologic compromise resulting from spinal cord compression.
primary chemotherapy
Neuroblastoma
In the POG experience for intermediate-risk patients,
what RT doses were given?
24 Gy/1.5 (2 years below)
30 Gy/1.5 (older)
Neuroblastoma
What are the 4 most active agents against intermediate-risk patients?
cyclophosphamide
doxorubicin
etoposide
carboplatin
Neuroblastoma
What is the monoclonal antibody against tumor-associated disialoganglioside GD2, that has been shown to have activity against neuroblastoma?
ch14.18
Neuroblastoma
What is the general management for patients with high-risk disease (according to COG guidelines)?
combine
induction chemotherapy, surgical resection,
autologous stem cell rescue, and radiation therapy to the primary site and select metastatic sites, 13-cis-retinoic acid and immunotherapy in an attempt to improve outcome
The current protocol utilizes a higher radiation total dose of 36 Gy for patients with gross residual disease at their primary sites.
Neuroblastoma
For primary site RT, what is the CTV?
post-induction chemotherapy tumor bed and residual tumor with 1 to 1.5 cm margin.
Neuroblastoma
For patients who had TBI as a preparative regimen for BMT were less likely to have relapse in prior sites of disease compared to those who did not have TBI.
TRUE or FALSE?
True
Li and colleagues
Neuroblastoma
In general, what is the RT dose given to the PTV (primary site)
The CTV and PTV are typically treated to 21.6 Gy in 12 fractions.
Neuroblastoma
Persistent activity in metastatic sites after induction therapy can be treated with radiotherapy as long as the patient can tolerate the treatment.
What is the dose?
The dose is 21.6 Gy in 12 fractions over 2.4 weeks and follows the same CTV and PTV guidelines for the primary site.
