NEUROBLASTOMA
 
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NEUROBLASTOMA

 

DEFINITION:

A tumour of post-ganglionic sympathetic neurons characterized by an abdominal mass and varied clinical manifestations.

EPIDEMIOLOGY:

  • prevalence: 1/10,000 live births
    • most common extracranial solid tumor in children
    • makes up 8-10% of all childhood cancer
  • age of onset:
    • median age - 2 years
    • 75% diagnosed by - 5 years
    • 97% diagnosed by - 10 years
  • risk factors:
    • familial - chrom.#: 1p36.2-p36.1
      • gene: ?
    • whites > blacks
    • males > females (1.2:1)

PATHOGENESIS:

1. Tumor Origin

  • 1. adrenal medulla (50%)
  • 2. extra-adrenal (sympathetic chain or ganglion)
    • below the diaphragm (30%)
      • in pelvic or visceral ganglia, paraganglia, or the organ of Zukerkandel
    • above the diaphragm (15-20%)
      • in cervical or thoracic sites

         

    • 70-80% have involved regional lymph nodes or metastases at more distant sites at presentation
    • tumor may regress or mature spontaneously (in 5-10% of cases)
    • about 20% of tumors are the result of a germinal mutation
    • a subset have an autosomal dominant pattern of inheritance

    • CLINICAL FEATURES:

    1. Primary Tumors

    1. Adrenal Medulla

    • abdominal mass and/or pain - firm, irregular, non-tender
    • anorexia, vomiting

    2. Extra-Adrenal

    • cervical ganglia - Horner syndrome, heterochromia
    • thoracic - dysphagia, dyspnea, infections, chronic cough
    • pelvic - difficulty with defecation or urination
    • paraspinal - back pain, paraplegia, stool/urine retention

    2. Metastases

  • 1. Bone Marrow - pain, pancytopenia
  • 2. Cortical Bone - pain (long bone); periorbital ecchymosis, proptosis (skull)
  • 3. Liver - hepatomegaly, distension
  • 4. Lung - dyspnea, infections
  • 5. Lymph Nodes - left supraclavicular, cervical, inguinal
  • 6. Skin - multiple subcutaneous bluish nodules

    • 3. Paraneoplastic Syndromes

  • 1. Angiotensin - hypertension (stretching of renal artery)
  • 2. Catecholamines - flushing, hypertension
  • 3. VIP Syndrome - watery diarrhea, distension
  • 4. Opsoclonus-Myoclonus Syndrome - myoclonic jerks; chaotic conjugate eye movements
  • 5.Progressive Cerebellar Ataxia

    • INVESTIGATIONS:

    1. Imaging Studies

    • Chest X-Ray, Abdominal X-Ray, skeletal survey, Abdominal ultrasound
    • CT - chest, abdomen
    • Body Scan - 131I-MIBG (taken up by neuroblasts)
    • Bone Scan - Tc-99 MDP

    2. Pathology

  • 1. Tumor
    • undifferentiated small, round, blue-cell tumor (also seen with Rhabdomyosarcoma and Ewings Sacroma)
    • karyotype, DNA index, N-myc copy number
  • 2. Bone Marrow
    • neuroblastoma, pancytopenia

    • 3. Biologic

  • 1. Urine
    • elevated homovanillic acid (HVA) and vanillymandelic acid (VMA) - 90-95% of tumors secrete catecholamines - elevated metanephrine and normetanephrine
  • 2. Serum
    • elevated levels of:
      • enolase (neuron-specific)
      • ferritin
      • LDH (represents tumor load)

    • STAGING:

    • International Neuroblastoma Staging System (1988)
    • Stages 1 - 4S

    POOR PROGNOSTIC INDICATORS:

    1. Clinical/Biologic

    • Stage IV
    • Stage III with
      • increased enolase (>100 ug/L)
      • increased ferritin (>142 ug/L)
      • increased LDH (>1500 IU/L)
      • increased N-myc copies
    • age >1 year
    • adrenal tumor
    • undifferentiated cells (with diploid DNA)
    • multiple N-myc copies
    • chronic 1p deletion

    MANAGEMENT:

    1. Surgery

    • primary and "second-look" operations

    2. Chemotherapy

    • mainstay of therapy
    • pairs and combinations of drugs used
    • has not had a significant impact in older patients
    • CCSG Protocol
      • cisplatinum
      • etoposide
      • adriamycin
      • cyclophosphamide

     

     

     

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