Neuroblastoma

Neuroblastoma
also Neuroblastoma, cervical (needs completion)

Location

70% Abdomen (ADRENALS or retroperitoneal in sympathetic chain) ; The primary site of neuroblastoma most commonly is the adrenal gland.
Nontender, firm, fixed, nodular abdominal mass; may be midline (unlike Wilm's tumor, which is smooth, and only occasionally cross midline)
Calcifications in 50% (vs Wilms, which usually does not calcify)
Other primary sites, in order of decreasing frequency, are the paravertebral retroperitoneum, posterior mediastinum, pelvis, and cervical area.
The presenting abdominal mass also may represent hepatic metastases, which can be massive.
Metastatic disease may be noted in several other sites, including skin, bone marrow, bone, and periorbital tissue.
Horner syndrome can be a complication of high thoracic and cervical masses.
Adrenocortical carcinomas involve the adrenal gland, but they are much less common than neuroblastomas.

Clinical Presentation

The family often identifies the mass, and such a complaint never should be ignored. With the occasional exception of a child who has constipation, this finding is almost always a true mass.
These children often appear chronically ill.
Often have severe bone pain out of proportion to physical exam
70% metastatic at diagnosis
Bone, bone marrow, liver, orbit, skin
NOT to lungs or brain (sites of high oxygen)
Raccoon Eyes due to bleeding of orbital metastases
Approximately 90% to 95% of neuroblastomas produce increased catecholamines, which can be measured by their urinary metabolites. 95% have elevated urinary HVA or VMA
Urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) are measured and compared to the excretion of creatinine in the sample. This allows the use of a "spot" sample and avoids the need for timed 24-hour collections that are very difficult to obtain.
Weight loss, Jitteriness, Flushing, Sleep Disturbance; Hypertension and Tachycardia
Secretory Diarrhea; Vasoactive intestinal peptide
Fevers
Opsoclonus/Myoclonus
- Rare paraneoplastic syndrome
- Chaotic eye movements, myoclonus & ataxia
- “Dancing eyes and dancing feet”
- Favorable biologic features and are likely to survive
- Associated with pervasive and permanent neurologic and cognitive deficits
- May be due to an autoimmune reaction
- Antineuronal antibodies cross-react with neural brain cells to cause acute cerebellar encephalopathy
- Steroids, IVIG or ACTH are thought to be effective

Presenting Syndromes Associated With Neuroblastoma

Pepper syndrome: massive involvement of the liver with metastatic disease with or without respiratory distress
Horner's syndrome: unilateral ptosis, myosis, and anhidrosis associated with a thoracic primary tumor. Symptoms do not recover with tumor removal.
Hutchinson's syndrome: limping and irritability in the young child associated with bone and bone marrow metastases
Opsomyoclonus: myoclonic jerking and random eye movement with or without cerebellar ataxia. May be associated with a differentiated, favorable outlook tumor, but sx may not resolve after tumor removal.
Kerner-Morrison syndrome: intractable secretory diarrhea associated with a biologically favorable tumor that secretes vasointestinal peptides. Sx always resolve with tumor removal.
"Racoon Eyes": Noted where there is periorbital hemorrhage secondary to metastatic tumor.

Further Evaluation

A thorough evaluation for metastatic disease should be performed prior to therapy:
Bilateral bone marrow
MIBG scan, regular bone scan
CT scan chest, abdomen, pelvis
Biopsy tumor or suspicious lymph nodes
LP not needed as CNS metastasis at diagnosis is rare

Staging: International Neuroblastoma Staging System (INSS)

Stage 1: localized tumor with complete gross excision; confined to organ
Stage 2: localized tumor with incomplete gross excision; extends beyond organ but not beyond midline
- 2A no ipsilateral lymph node involvement
- 2B with ipsilateral lymph node involvement
Stage 3: extends beyond midline
Stage 4: metastatic
Stage 4S:
- Age < 1yo
- Localized primary tumor at stage 1 or 2
- Dissemination limited to the liver, skin or bone marrow

Prognosis

Poor prognostic factors

Good prognostic factors

Treatment

Survival

Questions:

Answers

Neuroblastoma vs Wilms

Presentation: NB- sicker, Wilms - incidental mass
Age: NB younger (2 yo); Wilms older (3 yo)
metastases: NB - Bone, BM, liver, orbit, skin, NOT lungs or brain; Wilms: Bone, Liver, lungs, brain

CHLA Board Review 2005