Metastatic Neuroblastoma - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Cancer is a disease characterized by the uncontrolled growth of cells in the body. The disease can affect individuals of any age, including infants and children. New cells replace the old cells in a healthy body as they die. When problems arise in the normal cell cycle, new cells grow and ultimately form a mass. These masses or tumors can be benign (non-cancerous) or malignant (cancerous). Malignant tumors are more dangerous as they can invade local and distant organs. They also take a physical and mental toll on one’s health. Cancers occurring in childhood often develop without symptoms, but they can be well managed. Read this article below to learn more about neuroblastoma, a type of cancer occurring in children.

What Is Metastatic Neuroblastoma?

Understanding Neuroblastoma:

• Neuroblastoma is a cancerous tumor that arises from immature nerve cells called neuroblasts. These cells (neuroblasts) can be found in several body parts. It is the most common extracranial (outside the skull) solid cancer in children.

• Neuroblastoma can be present at birth, but they are not detected until symptoms appear.

• The tumor commonly develops in the chest, spine, neck, and abdomen (adrenal gland area).

• Children under five years of age are affected more compared to older children.

Metastatic Neuroblastoma:

• The original site of occurrence is called the primary neuroblastoma.

• Neuroblastoma in advanced stages starts to invade other body compartments. This is called metastasis.

• A category of neuroblastoma affects children below 18 months; this phase of cancer spreads to either the liver, skin, or bone marrow.

What Causes Metastatic Neuroblastoma?

Most neuroblastomas occur independently (99 % of the cases); however, a family history of neuroblastoma makes the child susceptible. An abnormality in chromosome 1 and having multiple copies of the gene MYCN (a gene that plays a key role in cell growth and division) in the tumor cells has been linked to neuroblastoma. Additionally, children with other birth defects are more likely to develop this cancer. Researchers also determine the relationship between maternal exposure to toxic substances during pregnancy and neuroblastoma. The occurrence of neuroblastoma is also linked to the following conditions:

• Beckwith-Wiedemann syndrome.

• DiGeorge syndrome.

• Hirschsprung disease.

• Neurofibromatosis type 1.

Routes of Metastasis:

The spread of cancer cells can happen through the following routes -

1. Blood circulation.

2. Lymph nodes and lymphatic network.

3. Local invasion.

What Are the Signs and Symptoms of Metastatic Neuroblastoma?

The signs and symptoms of neuroblastoma depend on the primary affected site and metastasis site.

1. Abdominal Neuroblastoma:

• Pain in the abdomen.

• A painless mass under the skin.

• Constipation or diarrhea (bowel movement changes).

2. Neuroblastoma in the Chest:

• Pain in the chest.

• Difficulty breathing and wheezing.

• Changes in the eyes (dropping of eyelids and pupil size abnormalities).

Other General Symptoms:

• Unexplained weight loss.

• Fatigue, weakness, and fever.

• Bloating.

• Signs of anemia (pale skin).

• Pain and weakness in the bones.

• Neurological symptoms such as uncoordinated and uncontrolled movements.

How Is Metastatic Neuroblastoma Diagnosed?

The following tests are recommended for the diagnosis of neuroblastoma:

1. Physical Examination and Medical History - The doctor physically examines the patient to check for lumps or masses. The patient’s history of illness and habits is also noted down.

2. Neurological Examination - The doctor also checks the functional status of the brain, spinal cord, nerves, and muscles. The patient’s mental status, coordination, senses, and reflexes are assessed.

3. Urine Chemistry - Certain substances like vanillylmandelic acid (VMA) and homovanillic acid (HVA) are higher than normal in neuroblastoma. These are breakdown products of catecholamines (hormones produced by the adrenal glands) and are assessed in urine tests.

4. Blood Chemistry - Certain substances called tumor markers are present in higher quantities and can be studied in blood samples.

5. MIBG (Iodine-123 Meta-Iodobenzylguanidine) Scan - The procedure is useful for detecting neuroblastoma. A radioactive substance, MIBG, is injected, and if the tumor is present, it will take up the substance. A scanner then detects the tumor.

6. Advanced Imaging - These techniques include computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) scans. The neuroblastoma can be visualized accurately, and the treatment can be carried out accordingly.

7. X-Ray - A conventional X-ray of the bone is taken to determine the metastasis.

8. Biopsy - A part of the tumor is removed using surgical tools, and the tissue is sent for microscopical analysis. A biopsy confirms the diagnosis after studying cancer cells specific to neuroblastoma.

What Is the Treatment for Metastatic Neuroblastoma?

1. Surgery - If the tumor is localized and not spread to other sites, surgery is the treatment of choice. The tumor, along with the lymph nodes, is removed.

2. Radiation Therapy - High energy radiation kills cancer cells or prevents them from multiplying further. The radiation source is given outside the body and is targeted at tumor cells.

3. MIBG Therapy - Radioactive iodine is given through a vein; it reaches the tumor cells; it kills them with the emitted radiation. This method is used in high-risk cases of neuroblastoma.

4. Chemotherapy - The treatment utilizes drugs (chemotherapeutic agents) that target cancer cells. These medications kill cancer cells by interfering with their cell cycle and can be given orally or intravenously.

5. Targeted Therapy - Drugs used for targeted therapy attack only the specific cancer cells, and the normal cells are spared. Targeted therapy has fewer side effects compared to other treatment modalities.

6. Immunotherapy - Substances that enhance or boost the body’s immune system to fight cancer cells are given. It is a type of biological therapy that uses the patient’s immune system to fight cancer.

What Are the Factors That Affect the Treatment Option and Prognosis?

• Age of diagnosis and stage of the tumor.

• Association with genetic changes.

• Response to initial treatment.

• Site of cancer.

• Recurrence of cancer after the treatment.

• Characteristics of cancer cells.

Survival Rate:

• The five-year survival rate of children with low-risk neuroblastoma is more than 95 %.

• The five-year survival rate of children with intermediate-risk neuroblastoma is around 90 % to 95 %.

• The five-year survival rate of children with high-risk neuroblastoma is around 50 %.

Conclusion:

Neuroblastoma is a cancer that originates from immature neural cells called neuroblasts. If these cancer cells invade local or distant organs, it is called metastatic neuroblastoma. Common sites of metastasis include the bone marrow, skin, and liver. Symptoms of metastatic neuroblastoma mainly depend on the primary site of origin and site of metastasis. Low-risk cases of metastatic neuroblastoma do not require treatment. However, high-risk cases are treated with surgery, chemotherapy, radiation therapy, immunotherapy, etc. Metastatic neuroblastoma can be treated early with minimal morbidity and mortality if detected early.