Neuroblastoma and Its Diagnosis
Sample
- 24 hours urine sample is recommended for the estimation of VMA (Vanillyl mandelic acid) because of its variety of secretion throughout the day.
- Collect urine in the sterile container containing acid HCl (10 ml) as a stabilizer.
- Measure the volume and keep 50 ml at 4 °C until the test is run or freeze for a longer period.
- Urine for 24 hours for HVA (homovanillic acid) is collected like VMA.
Definition
- This is a common tumor of the infancy and is extracranial.
- This is an embryonal malignancy of the sympathetic nervous system arising from the neuroblast.
- Neuroblastoma most commonly arises in and around the adrenal glands.
- Neuroblastoma can also originate in the abdomen, chest, neck, and near the spine.
- This tumor when is neural crest origin may arise anywhere in the sympathetic nervous system from the head to the pelvis.
- 75% arise within the abdomen.
- nearly 50% in the adrenal gland.
- Other 50% paravertebral autonomic ganglia.
- Origin in the brain is rare.
Pathophysiology
- Neuroblastoma >90% associated with increased production of:
- Catecholamines
- Catecholamines metabolites.
- There is increased excretion in the urine of:
- Norepinephrine.
- VMA.
- HVA.
- Dopamines.
- Dopamine excretion in the urine is increased in the Neuroblastoma.
- The precursor is L-Tyrosine which ultimately gives rise to Dopamine, Norepinephrine, and Epinephrine.
Signs and Symptoms
- It will affect children 5 years or younger age group.
- 80 to 90% of the cases are seen under the age of 5 years.
- This accounts for 15% of all childhood cancers death.
- It is rare for older children.
- The most common site is the adrenal medulla for the Neuroblastoma, but it can arise anywhere along with the sympathetic system.
- There may be abdominal pain.
- There may be mass under the skin but it is not tender.
- There may be changes in bowel habits, like diarrhea and constipation.
- While the neuroblastoma of the chest may give rise to wheezing and chest pain.
- The eyeball may be protruded from the sockets (proptosis).
- There may be dark circles and bruise around the eye.
- Other signs and symptoms may be seen as:
- Back pain.
- Bone pains.
- Fever.
- There unexplained weight loss.
- There is:
- Hypertension.
- Sweating.
- A headache.
- Tachycardia.
- These patients may have:
- Metastasis to lymph nodes, bone marrow, bone, skin, and liver.
- There may be hepatomegaly and ascites.
- The patient may have signs and symptoms due to the secretion of certain chemicals giving paraneoplastic syndrome.
- There may be spinal cord compression and this may lead to pain and paralysis.
- Metastasis to lymph nodes, bone marrow, bone, skin, and liver.
- 90% of the cases are associated with excessive production of catecholamines and catecholamine metabolites.
- So estimation of catecholamines helps :
- In the diagnosis.
- In the screening of this tumor.
- It helps to follow the treatment effect.
- Increased excretion of dopamine is characteristic of Neuroblastoma.
- So estimation of catecholamines helps :
- There is a unique feature in the natural history of this tumor, which is a spontaneous regression or sometimes therapy-induced maturation.
Normal
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
- A 24 hours urine sample is collected in a container containing HCl.
- 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) is also elevated in almost all cases.
- HVA is the main urinary metabolite of Dopa and Dopamine.
- This can be used for the diagnosis and the treatment follow-up of Neuroblastoma.
- 24 hours of the urine sample is collected.
- Add 10 mL of HCl (6 mol/L) for 24 hours sample.
- 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
- Urine Vanillylmandelic acid (VMA) is elevated almost in all cases. VMA is the end product of norepinephrine and epinephrine.
- VMA is the major catecholamine metabolite and it represents 60% of the total metabolites of Norepinephrine and Epinephrine.
- The more poorly-differentiated tumor produces more HVA than VMA.
- Other tumor markers which are nonspecific but used to follow tumor activity are:
- Neuron-specific enolase (NSE).
- Lactate dehydrogenase.
- Ferritin.
- Ultrasound, CT scan, and MRI may help in diagnosing the tumor.
- Biopsy of the tissue to confirm the diagnosis.
- Bone marrow aspiration may be advised to rule out infiltration by the tumor.
Treatment
- 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.
- In some cases, chemotherapy may be given. This may be given prior to the surgery to shrink the tumor.
- The third choice is radiotherapy.
Prognosis
- This depends upon the stage of the tumor and the age of the patients.
- Younger children under the age of one year have a better prognosis than older children.