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Neuroblastoma and Its Diagnosis

February 8, 2023Chemical pathologyLab Tests

Table of Contents

  • Neuroblastoma
      • Sample for Neuroblastoma
      • Definition of Neuroblastoma
      • Pathophysiology of Neuroblastoma
      • Signs and Symptoms of neuroblastoma:
      • Normal Adrenal gland’s hormone
      • VMA normal values
      • Homovanillic acid (HVA):
      • Diagnosis of neuroblastoma
      • Treatment of Neuroblastoma
      • Prognosis of Neuroblastoma
      • Questions and answers:

Neuroblastoma

Sample for Neuroblastoma

  1. 24 hours urine sample is recommended for the estimation of VMA  (Vanillyl mandelic acid) because of its variety of secretion throughout the day.
    1. Collect urine in the sterile container containing acid HCl (10 ml) as a stabilizer.
    2. Measure the volume and keep 50 ml at 4 °C until the test is run or freeze for a longer period.
  2. Urine for 24 hours for HVA (homovanillic acid) is collected like VMA.

Definition of Neuroblastoma

  1. This is a common tumor in infancy and is extracranial.
  2. This is an embryonal malignancy of the sympathetic nervous system arising from the neuroblast.
  3. Neuroblastoma most commonly arises in and around the adrenal glands.
  4. Neuroblastoma can also originate in the abdomen, chest, neck, and near the spine.
    1. This tumor, when is neural crest origin, may arise anywhere in the sympathetic nervous system from the head to the pelvis.
    2. 75% arise within the abdomen.
      1. Nearly 50% in the adrenal gland.
      2. Other 50% paravertebral autonomic ganglia.
      3. Origin in the brain is rare.

Pathophysiology of Neuroblastoma

  1. Neuroblastoma >90% associated with increased production of:
    1. Catecholamines.
    2. Catecholamines metabolites.
Adrenal glands catecholamine

Adrenal glands catecholamine

  1. There is increased excretion in the urine of:
    1. Norepinephrine.
    2. VMA (Vinyl mandelic acid)
    3. HVA (Homovanilic acid).
    4. Dopamines.
  2. Dopamine excretion in the urine is increased in Neuroblastoma.
Dopamine metabolism

Dopamine metabolism

  1.  The precursor is L-Tyrosine which ultimately gives rise to Dopamine, Norepinephrine, and Epinephrine.
Catecholamine formation

Catecholamine formation

Signs and Symptoms of neuroblastoma:

  1. It will affect children 5 years or younger age group.
    1. 80 to 90% of the cases are seen under the age of 5 years.
    2. This accounts for 15% of all childhood cancers death.
  2. It is rare for older children.
  3. The most common site is the adrenal medulla for Neuroblastoma, but it can arise anywhere along with the sympathetic system.
Adrenal glands medulla hormone

Adrenal gland’s medulla hormone

Adrenal gland hormones

Adrenal gland hormones

  1. There may be abdominal pain.
    1. There may be a mass under the skin, but it is not tender.
    2. There may be changes in bowel habits, like diarrhea and constipation.
  2. While the neuroblastoma of the chest may give rise to wheezing and chest pain.
    1. The eyeball may be protruded from the sockets (proptosis).
    2. There may be dark circles and bruise around the eye.
  3. Other signs and symptoms may be seen as:
    1. Back pain.
    2. Bone pains.
    3. Fever.
    4. There is unexplained weight loss.
  4. There is:
    1. Hypertension.
    2. Sweating.
    3. A headache.
    4. Tachycardia.
  5. These patients may have:
    1. Metastasis to lymph nodes, bone marrow, bone, skin, and liver.
      1. There may be hepatomegaly and ascites.
    2. The patient may have signs and symptoms due to the secretion of certain chemicals giving paraneoplastic syndrome.
    3. There may be spinal cord compression, leading to pain and paralysis.
  6. 90% of the cases are associated with excessive production of catecholamines and catecholamine metabolites.
    1. So estimation of catecholamines helps :
      1. In the diagnosis.
      2. In the screening of this tumor.
      3. It helps to follow the treatment effect.
      4. Increased excretion of dopamine is characteristic of Neuroblastoma.
  7. There is a unique feature in the natural history of this tumor, which is a spontaneous regression or sometimes therapy-induced maturation.

Normal Adrenal gland’s hormone

Patient position Norepinephrine pg/mL Epinephrine pg/mL Dopamine pg/mL
Sitting for 15 minutes 120 to 680 <60 <87
Standing for 30 minutes 125 to 700 <90 <87
Supine for 30 minutes 110 to 410 <50 <87

VMA normal values

  1. A 24-hour urine sample is collected in a container containing HCl.
  2. 10 mL of HCl, 6 mol/L for 24 hours of the urine sample is required.
Age of the patient VMA mg/day VMA mg / g Creatinine 
3 to 6 years 1.0 to 2.6 4.0 to 10.8
6 to 10 years 2.0 to 3.2 4.0 to 7.5
10 to 16 years 2.3 to 5.2 3.0 to 8.8
16 to 83 years 1.4 to 6.5

Homovanillic acid (HVA):

  1. It is also elevated in almost all cases.
  2. HVA is the main urinary metabolite of Dopa and Dopamine.
  3. This can be used for the diagnosis and the treatment follow-up of Neuroblastoma.
  4. 24 hours after the urine sample is collected.
    1. Add 10 mL of HCl (6 mol/L) for 24 hours sample.
    2. Normal values in the urine  are:
Age of the patient HVA mg/day HVA mg/ g Creatinine 
3 to 6 years 1.4 to 4.3 5.4 to 15.5
6 to 10 years 2.1 to 4.7 4.4 to 11.5
10 to 16 years 2.4 to 8.7 3.3 to 10.3
16 to 80 years 1.4 to 8.8

Diagnosis of neuroblastoma

  1. Urine Vanillylmandelic acid (VMA) is elevated almost in all cases. VMA is the end product of norepinephrine and epinephrine.
  2. VMA is the major catecholamine metabolite, and it represents 60% of the total metabolites of Norepinephrine and Epinephrine.
  3. The more poorly-differentiated tumor produces more HVA than VMA.
  4. Other tumor markers which are nonspecific but used to follow tumor activity are:
    1. Neuron-specific enolase (NSE).
    2. Lactate dehydrogenase.
    3. Ferritin.
  5. Ultrasound, CT scan, and MRI may help in diagnosing the tumor.
  6. Biopsy of the tissue to confirm the diagnosis.
  7. Bone marrow aspiration may be advised to rule out infiltration by the tumor.

Treatment of Neuroblastoma

  1.  The first choice is surgery. One can remove the whole tumor. Still, surgery may be needed for surgical pathology to know the grade of the tumor.
  2. In some cases, chemotherapy may be given. This may be given prior to the surgery to shrink the tumor.
  3. The third choice is radiotherapy.

Prognosis of Neuroblastoma

  • This depends upon the tumor stage and the patient’s age.
  • Younger children under the age of one year have a better prognosis than older children.

Questions and answers:

Question 1: How you will diagnose neuroblastoma?
Show answer
Urine VMA will be raised.
Question 2: What other hormone will be raised in poorly differentiated neuroblastoma?
Show answer
Along with VMA, there is raised level of Homovanillic acid (HVA).

Possible References Used
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