Neuroblastoma is a tumor of neural crest cell origin seen predominantly in children. It has been the subject of a great deal of study because it may be rapidly progressive, or in other cases spontaneous regress. It is most common in first 2 years of life with 35% found in children <1 year of age and 5% occur in children >10 years of age

Epidemiology
Neuroblastoma is the most common solid abdominal malignancy in children. It accounts for 6-10% of all childhood malignancies and 15% of cancer-related deaths in children. Neuroblastoma occurs in 1/10,000 live births (~525 new cases / year).

Locations
•Most often arise from adrenals (but can occur anywhere along the sympathetic chain)
– 75% found in abdomen or pelvis (>50% near adrenals)
– 20% within posterior mediastinum
– 5% in neck

Presentation
Most common presentation is as an asymptomatic mass
– Presentation depends on location
– If abdominal, may present w/ abdominal pain, distention, Failure to thrive/weight loss, or anorexia
– If in neck, may present as palpable or visible mass
– Posterior mediastinal locations most often present w/ pneumonia, dyspnea, or Horner’s syndrome with the mass identified on CXR
– Some tumors extend into neural foramina and causing cord compression or paraplegia.

Exam
– Palpable mass in abdomen if large
– Hepatomegaly if metastasis to liver
– “Blueberry muffin” skin lesions
– “Raccoon eyes” w/ orbital metastasis, along w/ proptosis

Paraneoplastic Syndromes
– “Dancing eyes & feet” –> cerebellar ataxia, involuntary movements, and nystagmus
– Diarrhea –> excess secretions of VIP
– Hypertension –> excess catecholamine secretion

Metastatic Spread
– Cortical bone, bone marrow, lung, and liver

Diagnosis
– History & physical exam
– Labs
– CBC, BMP, LFTs
– Urine catecholamine metabolites (specifically homovanillic and vanillylmandelic acid)
– Serum LDH >1500 IU/mL
– Serum ferritin >152 ng/mL
– Neuron-specific enolase (NSE) >100 ng/mL

Imaging
– CT and/or MRI preferred
– Bone scan to identify bone mets
– MIBG scan best for identifying mets
– Bone marrow biopsy for staging

Diagnosis
Tissue for histology
– Although imaging oftentimes points to unresectability, a tissue diagnosis is still needed
– Cytogenetic studies aid in prognosis
– Amplification of N-myc is associated w/ rapidly progressing disease and poor

Staging
See the NCI (www.cancer.gov) website or American Cancer Society for current staging

Treatment
Surgery
– Surgical resection of primary tumor + adjacent LNs is goal
– May be curative in localized Stage 1 and 2 disease
– For “unresectable disease” –> incisional biopsy, with re-evaluation for resection after adjuvant therapies administered
– Requires oftentimes difficult dissection around major vessels that course through tumor
Chemotherapy
Radiation Therapy
Immunotherapy

The Special Case for Stage I Neuroblastoma
(from May/June 2000, Journal of Pediatric Hematology/Oncology)
Prospective evaluation of 329 patients w/ stage 1 neuroblastoma, who underwent surgery alone for therapy
– Event Free Survival (EFS) = 91%, overall survival = 96%
– Lower survival found in patients w/ high N-myc counts, age older than 12 months
– Site of tumor had no impact on survival
– Diploid tumors –> 82% EFS, but w/ surgery –> 100% survival.
– Unfavorable histology –> 80% survival
– High N-myc amplification –> 64% survival

Prognosis
Depends on stage, histologic factors, and age
• Broken into risk groups – low, intermediate, and high

Low
– Stage 1
– Stage 2 (<1 year of age, >1 year of age but low N-myc, or >1 year w/ favorable histology
– Stage 4S (w/ favorable histology)
– Survival >90%

Intermediate
– Stage 3 (<1 year of age w/ low N-myc, or >1 year of age w/ favorable histology)
– Stage 4 (<1 year w/ low N-myc)
– Stage 4S (w/ low N-myc)
– Survival ~80%

High
– Stage 2 (>1 year, unfavorable histology)
– Stage 3 (<1 year w/ high N-myc, >1 year w/ unfavorable histology)
– Stage 4 (<1 year w/ high N-myc, >1 year regardless of histology or N-myc)
– Stage 4S (w/ high N-myc)
– Survival 10-20%

Prognosis
– Gain of genetic material from chromosome 17q –> associated w/ poor outcome
– Diploid tumors –> poorer prognosis…but hyperdiploid tumors –> better prognosis

– Expression of TRK proto-oncogene –> more favorable prognosis

Sources

American Cancer Society (www.cancer.org)
National Cancer Institue (www.cancer.gov)
Alvarado, Carlos, etc. al. “Natural History and Biology of Stage A Neuroblastoma: A Pediatric Oncology Study Group.” Journal of Pediatric Hematology/Oncology. May/June 2000