Neuroblastoma


Introduction:
It is the second most common solid tumor in children after brain tumor. It occurs in the neural crest cells, called neuroblasts, of the sympathetic nervous system. It can occur in a number of anatomical sites. The majority of tumors (65%) are located in the abdomen, often in one of the two adrenal glands. However, primary tumors can occur anywhere in the body. Other common sites are the chest, neck or pelvis. It is one of the most malignant neoplasms of children & rarely seen in adults.


Incidence:
Neuroblastoma represents 7.5% of all childhood cancers. It is most commonly diagnosed between 17 months and 2 years of age.

Aetiology:
Neuroblastoma develops when normal neuroblasts (the immature cells of the sympathetic nervous system) fail to mature into nerve cells. Instead, they continue to grow leading to mass of cancer cells.

Other hypothesis is “mutations” occurring in Neuroblastoma cells.

Symptoms:
Symptoms of Neuroblastoma are dependent upon the site, metastatic disease or associated paraneoplastic syndromes,

Abdominal distention/constipation
Pain in the abdomen.
Fever, bony pain, anemia, if the disease has spread to the bone marrow, causing a decrease in red blood cells.
Bulging, darkening, proptosis or swelling of the eye, if the disease has spread to tissues and bone around the eyes.
Persistent diarrhea, high blood pressure, palpitations, reddening of the skin, sweating, involuntary movements of eyes & limbs, if there is associated paraneoplastic syndrome

Investigations:

Complete blood count
Biochemistry including serum LDH & serum ferritin
Bone marrow aspiration & Biopsy
Urinary VMA (Vanillyl mandelic acid) and HMV (Homovanillic acid)
N-myc amplification
DNA index
MIBG (131I-meta-iodobenzyl guanidine) scan
Chest X-Ray
CT Scan of primary region
MRI spine ( If neurological symptoms)
Bone scan
Biopsy of the tumor

Prognostic factors:

Age of the child
Stage of the disease
Tumor Histopathology
Myc-N Status
DNA Index (Ploidy)


Treatment:

Induction Chemotherapy: Multi-drug chemotherapy is first given to try to reduce the size of the primary and metastatic tumor(s). The drugs used are cyclophosphamide, doxorubicin, cisplatin, etoposide, Ifosphamide.

Surgery: Surgery is done to remove as much tumor as safely possible. In some locations its possible to remove whole mass

Radiation Therapy: It is usually given locally to the tumor site.

Myleoablative therapy followed by stem cell or bone marrow transplant: Intensive doses of chemotherapy to eliminate any remaining tumor cells, followed by an autologous peripheral blood stem cell transplant, or sometimes a bone marrow transplant, to restore the immune system is used in high risk disease.

Minimum residual disease therapy: Additional drugs like 13-cis-Retinoic acid, aimed at eliminating or altering minimal residual disease is given after consolidation therapy.

MIBG Therapy: It is used when surgery is not possible because of persistent bone marrow disease after induction chemotherapy.

Prognosis:

Low risk patients have a greater than 90% survival.
Intermediate risk patients have a 70-90% chance of survival.
High risk patients have a 30% chance of survival

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