Neuroblastoma

John P. Christodouleas and Moody D. Wharam, Jr.

Background

What are the 3 types of neuroblastic tumors?

3 types of neuroblastic tumors:

Neuroblastoma (NB)
Ganglioneuroblastoma
Ganglioneuroma

These tumors differ in the degree of cellular maturation.

What is the most common malignancy in infants?

NB is the most common malignancy in infants.

Estimate the annual incidence of NB in the U.S.

There are ~650 cases/yr of NB in the U.S.

What is the median age at Dx for NB?

The median age at Dx is 17 mos.

Name 3 genetic syndromes associated with NB.

3 genetic syndromes associated with NB:

NF
Hirschsprung Dz
Fetal hydantoin syndrome

What tests have been used to screen infants for NB?

Historically, infants were screened for NB using–urinary catecholamines (vanillylmandelic acid/homovanillic acid).

Does screening improve survival in NB?

This is controversial. Screening infants for NB with urinary catecholamines has been evaluated in multiple studies; however, the value of catecholamine-based screening is limited by its false+ rate and b/c a significant % of infant NBs spontaneously regress.

What markers distinguish NB from other small round blue tumors?

NB-specific markers:

Neuron-specific enolase
Synaptophysin
Neurofilament

What is the cell of origin for NB?

NB arises from neural crest cells of the sympathetic ganglion.

What % of NB pts have detectable urinary catecholamines?

90% of pts have detectable urinary catecholamines.

What genetic changes are associated with n-myc amplification?

Double-minute chromatin bodies and homogeneously staining regions are associated with n-myc amplification.

What are the genetic/chromatin changes that portend a poor prognosis in NB?

Genetic/chromatin changes with a poor prognosis in NB:

N-myc amplification
LOH 1p + 11q
Diploid DNA
↑ telomerase activity

In which pts does DNA content not have prognostic importance?

DNA content does not have prognostic importance in metastatic pts.

What % of NB pts present with n-myc amplification?

30%–40% of pts present with n-myc amplification.

What % of NB pts present with 1p deletions?

70% of pts present with 1p deletions.

What is the genetic variation on 6p22 that is associated with clinically aggressive NB?

Homozygosity for 3 single nucleotide polymorphisms on 6p22 is associated with stage IV Dz, n-myc amplification, and Dz relapse. (Maris JM et al., NEJM 2008)

What are the most common sites of presentation for NB?

Adrenal medulla > paraspinal > post mediastinum

In what age group is thoracic presentation of NB more common?

Thoracic NB is more common in infants.

How does NB presentation differ from Wilms?

There are more systemic Sx in NB. (Mnemonic: Wilms are Well, Neuroblastomas are Not well)

What are some presenting Sx of NB?

Along with the presentation of a mass, NB may be associated with constitutional Sx (fever, malaise, pain, weight loss), periorbital ecchymosis (“raccoon eyes”), “blueberry muffin” sign (nontender blue skin mets), scalp nodules, bone pain, irritable/ill appearance, diarrhea (↑ vasoactive intestinal peptide), Horner syndrome, opsomyoclonus truncal ataxia (rare paraneoplastic syndrome of ataxia, random eye movement, and myoclonic jerking associated with early stage but persists after cure), and Kerner-Morrison syndrome (diarrhea, low K).

What % of NB pts present with mets?

75% of all NB pts present with mets.

A 2 yo presents with an abdominal mass and lung mets. What is the most likely Dx?

Wilms. NB rarely metastasizes to the lungs!

What are the most common sites of mets for NB?

NB commonly metastasizes to bone (~ 50%), LNs (35%), BM, liver, skin, and orbits. Lung mets are rare.

What are the most common bony sites of metastatic Dz in NB?

Bones of the skull and orbit (proptosis, ecchymosis, scalp mass)

Which is more likely to exhibit calcifications on x-ray: Wilms or NB?

NB (85%) is more likely to exhibit calcifications.

What are the classic histologic findings seen in NB?

Homer-Wright pseudorosettes, hemorrhage, and calcification