Neuroblastoma Flashcards by Mario Luna

Pediatric Maligancies

BONUS:

What is the most common extracranial tumor of childhood?

Neuroblastoma

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Neuroblastoma

Infant screening led to a decrease in the mortality rates when compared to non-screened control population.

TRUE or FALSE?

True

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What urinary metabolites can be quantitatively assayed by HPLC and normalized to urinary creatinine to detect for neuroblastoma?

homovanillic acid (HVA)
vanillylmandelicacid (VMA)

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Neuroblastoma

What urinary metabolite of epinephrine can be qualitatively to detect for neuroblastoma?

vanillylmandelicacid (VMA)

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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%)

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Neuroblastoma

What are the most common sites of metastases?

lymph nodes,
bone
bone marrow
skin

(lung and cns are rare sites)

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NB may spontaneously regress to a mature ______?

ganglioneuroma

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What is the most common presenting symptom?

pain

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Neuroblastoma

What “sign” is the term used to describe the skin metastases due to its tinge?

blueberry muffin sign

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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

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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.

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A ratio of VMA to HVA >1.5 is associated with an unfavorable prognosis in patients with metastatic neuroblastoma.

TRUE or FALSE?

False.

Favorable.

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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

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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

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Neuroblastoma

In imaging/staging of NB, what modality often overstages stage I tumors?

MRI

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In imaging/staging of NB, what modality often understage stage II tumors?

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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)

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Neuroblastoma

Identify the INSS stage:

Localized tumor with incomplete gross excision;

representative ipsilateral nonadherent lymph nodes negative for tumor microscopically

INSS Stage 2A

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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

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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

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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

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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.