Early symptoms of neuroblastoma

The early symptoms of neuroblastoma are sometimes ambiguous and may include irritability, fatigue, appetite loss, and fever. There are several factors conspiring to make this condition difficult to detect. First of all, the same symptoms may be caused by a different condition. Second, neuroblastoma is a rare type of cancer – even though it is the most common form of cancer in children. And third, patients may not show any symptoms at all. The symptoms depend on where the cancer is located and are usually caused by pressure from the tumor or bone pain if the cancer has metastasized to the bones.

Signs of neuroblastoma include:


Chest or neck

·         Abdominal pain

·         A lump under the skin that is tender to the touch

·         Changes in bowel habits (e.g. diarrhea)

·         Leg swelling

·         Decreased appetite

·         Wheezing

·         Difficulty breathing

·         Chest pain

·         Swelling in the face, neck, arms, and upper chest.

·         Headache

·         Dizziness

·         Changes to the eyes (dropping eyelids, unequal pupil size)

·         Horner’s syndrome


Other potential symptoms are:

·         Subcutaneous lumps of tissue.

·         Seemingly protruding eyeballs.

·         Dark circles around the eyes.

·         Back pain.

·         Unexplained loss of weight.

Additionally, the child may limp, refuse or become unable to walk, and if they are old enough, complain of feeling full. However, the seed of neuroblastoma is planted long before the child is even born. Neuroblasts are undeveloped cells found in fetuses which normally mature and become functional nerve cells or adrenal medulla cells before birth. Babies may be born with a few neuroblasts that either mature later or disappear. There is also the possibility that these neuroblasts neither mature nor stop growing, eventually forming a tumor. Neuroblastoma frequently begins in the tissue of the adrenal glands but is often only detected after it has spread to the lymph nodes, liver, lungs, bones, bone marrow, and other parts of the body.

Unfortunately, screening has not proven successful in diagnosing neuroblastoma. For example, testing 6 month old infants has found many tumors that would have normally escape detection, but most would have disappeared or matured into benign tumors anyway. Thus the only result was to unnecessarily distress parents and test and operate on children. Even when neuroblastoma is found early, it is mostly by accident, through a prenatal ultrasound or while performing tests to detect other children’s conditions. Therefore, screening for neuroblastoma is not recommended in low-risk children. As it turns out, though, the main – if not only – risk factor is heredity, and that only accounts for 1%-2% of cases.

As such, it is advised that parents call a pediatrician if their child shows any of the early symptoms of neuroblastoma. The doctor will perform a physical exam to check for signs and ask the parents about the child’s habits. The physician may also conduct specific tests such as an MIBG scan (MIBG – or meta-iodobenzylguanidine – is a protein that neuroblastoma absorbs, and this test can help find tumors in the bone, bone marrow, and other body parts) or blood and urine catecholamine tests (neuroblasts can make enough hormones called catecholamines to be detected in the blood or urine). Additional lab and imagine tests include:

·         Biopsy.

-        Bone marrow aspiration biopsy.

-        Incisional biopsy.

-        Needle biopsy.

·         X-ray

·         Ultrasound.

·         CAT scan.

·         MRI

·         Bone scan.

·         PET scan.

Testing can help determine the stage of the tumor (size, location, spread, etc.) and the risks it poses. There are two systems to stage a neuroblastoma; the International Neuroblastoma Staging System Committee (INSS) system and the International Neuroblastoma Risk Group Staging System (INRGSS).

Neuroblastoma staging systems






Tumor can be fully removed with surgery. Nearby lymph nodes are cancer-free.


Tumor is confined to area where it started (neck, chest, or abdomen).


Tumor is still where it started but can’t be fully removed with surgery. Nearby lymph nodes are cancer-free.


Tumor has not spread beyond original area but image-defined risk factors are present.


Tumor is still where it started and may or may not be fully removed with surgery. Nearby lymph nodes are cancer-free.


Tumor has spread to other parts of the body.


Tumor can’t be surgically removed, has spread to nearby lymph nodes, but not to other parts of the body.


Tumor has spread only to the skin, liver, and/or bone marrow in children under 18 months.


Tumor has spread to distant lymph nodes, bones, bone marrow, liver, skin, or other organs.



Tumor has spread only to the skin, liver, and/or bone marrow in children under 1 year.



The INRG and the Children’s Oncology Group (COG) use certain factors to classify a neuroblastoma as low, intermediate, or high risk.

Risk group criteria



·         Stage of disease per INRG system.

·         Age when diagnosed.

·         Histologic category*.

·         How similar tumor and normal cells are.

·         MYCN gene status**.

·         Changes to chromosome 11q.

·         DNA content of tumor cells (ploidy***).

·         Stage of disease per INSS system.

·         Age when diagnosed.

·         MYCN gene status.

·         DNA content of tumor cells (only for children under 18 months).

·         Tumor hispathology.

*Tumor histology is based on how the neuroblastoma appears on a microscope slide.

**MYCN is an oncogene that helps to regulate cell growth. Tumors with too many copies (see amplification below) of this gene grow quickly and are less likely to mature.

***The amount of DNA in each cell can be gauged with a flow cytometry, an imaging cytometry and other special lab tests. Hyperdiploidy (see below), or cells with high concentrations of DNA, is associated with early stages, better response to chemotherapy, and a more positive prognosis.




Low-risk neuroblastoma

·         Stage 1.

·         Stage 2A or 2B with over 50% of the tumor surgically removed (except for a child with MYCN amplification).

·         Stage 4S, no MYCN amplification, favorable histopathology, and hyperdiploidy.






Intermediate-risk neuroblastoma

·         Stage 2A or 2B, no MYCN amplification, with less than 50% of the tumor surgically removed.

·         Stage 3 in children under 18 months, no MYCN amplification.

·         Stage 3 in children over 18 months, no MYCN amplification, favorable histopathology.

·         Stage 4 in children under 12 months, no MYCN amplification.

·         Stage 4 in children aged 12-18 months, no MYCN amplification, hyperdiploidy, favorable histology.

·         Stage 4S disease, no MYCN amplification, unfavorable histopathology and/or diploidy.

High-risk neuroblastoma

·         Stage 2A or 2B, MYCN amplification.

·         Stage 3, MYCN amplification.

·         Stage 3 in children aged 18 months or older, no MYCN amplification, unfavorable histopathology.

·         Stage 4 in children under 12 months, MYCN amplification.

·         Stage 4 in children aged 12-18 months old, MYCN amplification, and/or diploidy, and/or unfavorable histology.

·         Stage 4 in children 18 months or older.

·         Stage 4S, MYCN amplification.

Some patients make a full recovery with surgery or surgery and chemotherapy, while others have a more aggressive form of neuroblastoma. Most will both treatments, though; this is because neuroblastoma has typically spread before it’s found, so it’s not possible to remove the entire tumor and any remaining cancer cells must be destroyed with drugs.

Neuroblastoma chemotherapy drugs

Intermediate risk

High risk

·         Carboplatin

·         Cyclophosphamide

·         Doxorubicin

·         Cyclophosphamide

·         Ifosfamide

·         Cisplatin

·         Vincristine

·         Doxorubicin

·         Melphalan

·         Etoposide

·         Topotecan

·         Busulfan

·         Carboplatin

·         Cytokines

·         Isotretinoin

Other treatment options include:

·         Radiation therapy.

·         Stem cell transplant.

·         Bone marrow transplant.

·         Immunotherapy

·         Retinoid therapy.

·         Targeted delivery of radionuclides.