Neuroblastoma: Symptoms, Causes, Treatment

What are the symptoms of neuroblastoma?

Neuroblastoma is a type of cancer that develops from immature nerve cells (neuroblasts) and most commonly occurs in infants and young children. The symptoms of neuroblastoma can vary depending on the tumor’s location, size, and whether it has spread (metastasized) to other parts of the body. Here are some common symptoms associated with neuroblastoma:

1. Common Symptoms:

• Abdominal Mass: A palpable mass or lump in the abdomen is one of the most common symptoms. This may be discovered during a routine examination or when the child exhibits other symptoms.
• Pain: Children may complain of abdominal, back, or bone pain, depending on the tumor’s location.
• Changes in Bowel or Bladder Function: If the tumor compresses nearby structures, it may lead to constipation or difficulty urinating.

2. Symptoms Based on Tumor Location:

• Adrenal Gland Tumors:
• Neuroblastomas often arise in the adrenal glands. Symptoms may include a visible lump in the abdomen, weight loss, or a rapid increase in blood pressure (hypertension).
• Neck Tumors:
• Tumors in the neck can cause swelling, a lump near the collarbone, or changes in voice and difficulty swallowing.
• Chest Tumors:
• If the tumor is located in the chest, symptoms may include difficulty breathing, persistent coughing, or chest pain.

3. Metastatic Symptoms:

• Bone Pain or Limps: If the neuroblastoma spreads to the bones, it can cause pain in the bones or joint pain, leading to limping or refusal to walk.
• Swelling: If lymph nodes are involved, swelling may occur in various areas of the body.

4. Other General Symptoms:

• Fatigue: Unexplained tiredness or lack of energy is common in children with neuroblastoma.
• Fever: Persistent or unexplained fever may occur.
• Night Sweats: Some children may experience heavy sweating at night.
• Weight Loss or Loss of Appetite: A decrease in appetite or significant weight loss is often reported.
• Bruising or Anemia Signs: Some children might develop unexplained bruises or signs of anemia, like pale skin.

5. Symptoms Associated with “Paraneoplastic Syndromes”:

• In some cases, neuroblastoma can produce hormones or other substances that lead to additional symptoms:
• Horner’s Syndrome: If the tumor affects the sympathetic nerves around the eyes, it can cause drooping eyelids, constricted pupils, and an absence of sweating on one side of the face.
• Increased Blood Pressure and Sweating: Due to catecholamine production, children may experience increased blood pressure or excessive sweating.

Conclusion:

The symptoms of neuroblastoma can be nonspecific and similar to other common childhood illnesses, making early diagnosis challenging. If a parent or caregiver notices persistent signs such as abdominal pain, unexplained lumps, or significant changes in behavior, it is critical to seek medical evaluation. Early diagnosis and treatment significantly improve the prognosis for children with neuroblastoma. If neuroblastoma is suspected, a healthcare provider may conduct imaging studies and other diagnostic tests to confirm the diagnosis and determine the appropriate treatment plan.

What are the causes of neuroblastoma?

The exact causes of neuroblastoma are not fully understood, but several factors have been identified that may contribute to the development of this type of cancer. Neuroblastoma originates from immature nerve cells (neuroblasts) and most commonly occurs in infants and young children. Here are some of the known risk factors and potential causes associated with neuroblastoma:

1. Genetic Factors:

• Familial Neuroblastoma: A small percentage of neuroblastoma cases are hereditary. Genetic mutations that increase the risk of neuroblastoma can be passed down through families.
• NMYC Gene Amplification: Abnormalities in the NMYC gene, which regulates cell growth and division, are often found in high-risk neuroblastomas. NMYC amplification is associated with aggressive tumor behavior.
• Chromosomal Abnormalities: Certain chromosomal changes or abnormalities, such as deletions in chromosome 1p or 11q, have been linked to neuroblastoma.

2. Developmental Factors:

• Neuroblast Development: Neuroblastoma is thought to arise from neuroblasts that fail to mature properly during fetal development. The tumor can develop from neuroblasts in various parts of the body, including the adrenal glands, sympathetic nervous system, and peripheral nerves.

3. Age:

• Infancy and Early Childhood: Neuroblastoma is most common in infants and children under the age of 5. The average age at diagnosis is around 18 months. The condition is rare in older children and adults.

4. Environmental Factors:

• Exposures During Pregnancy: Some studies have investigated environmental factors during pregnancy, such as exposure to certain chemicals or pesticides, raised concerns about risk, but the evidence is not conclusive.
• Infections and Immune Response: Infections during pregnancy or in early childhood may influence the risk of neuroblastoma, although specific causative agents have not been identified.

5. Ethnic and Racial Factors:

• Variability in Incidence: Neuroblastoma shows variability in incidence among different ethnic and racial groups. For example, it is more common in children of African descent compared to those of Asian descent. The reasons for these disparities are not yet clear.

6. Non-genetic Risk Factors:

• Gender: Neuroblastoma is somewhat more common in boys than girls, though the reasons for this difference are not well understood.

Conclusion:

While certain genetic and developmental factors increase the risk of neuroblastoma, the exact causative mechanisms remain largely unknown. Research continues to explore the interplay of genetic predisposition, environmental influences, and developmental processes in the formation of neuroblastoma. If there is a family history of neuroblastoma or related tumors, genetic counseling may be recommended to assess potential risks for future generations. Monitoring and early diagnosis are crucial for improving outcomes in affected children.

How is the diagnosis of neuroblastoma made?

The diagnosis of neuroblastoma typically involves a combination of clinical evaluation, imaging studies, laboratory tests, and sometimes biopsy. Here is a comprehensive approach used to diagnose neuroblastoma in children:

1. Clinical Evaluation:

• Medical History: The healthcare provider will take a detailed medical history, including any symptoms the child is experiencing, such as abdominal pain, a lump or mass, changes in appetite, weight loss, or other signs.
• Physical Examination: A thorough physical examination may reveal masses in the abdomen or other areas, signs of pain, neurological deficits, or other symptoms indicative of neuroblastoma.

2. Imaging Studies:

Several imaging techniques are used to visualize the tumor and assess its extent:

• Ultrasound: Often the first imaging test performed if a mass is suspected, particularly in the abdomen. It can help identify the tumor and assess its characteristics.
• Computed Tomography (CT) Scan: A CT scan of the abdomen and pelvis is commonly used to evaluate the size and location of the tumor and to check for any spread (metastasis) to nearby organs or lymph nodes.
• Magnetic Resonance Imaging (MRI): MRI may be utilized for better visualization of the tumor, especially in cases where the tumor is near the spine or brain.
• MIBG Scintigraphy: This specialized scan uses a radioactive substance that is taken up by neuroblastoma cells. It can help identify tumors and metastases in the body.

3. Laboratory Tests:

• Urine Tests: Measurement of catecholamines and their metabolites (such as vanillylmandelic acid (VMA) and homovanillic acid (HVA)) in the urine can be indicative of neuroblastoma. Elevated levels of these substances are often present in children with the disease.
• Blood Tests: Other blood tests may include checking for a complete blood count (CBC) and chemistry panels to assess overall health and detect any abnormal indicators.

4. Biopsy:

• Tissue Sampling: A definitive diagnosis of neuroblastoma typically requires a biopsy of the tumor. This can be performed through:
• Fine Needle Aspiration (FNA): A thin needle is used to extract a small sample of tissue from the tumor, which can be examined under a microscope.
• Core Needle Biopsy: A larger sample may be taken for better evaluation.
• Surgical Biopsy: In some cases, surgery may be necessary to remove part or all of the tumor for pathological examination.

5. Pathological Examination:

• Microscopic Evaluation: The biopsy sample is examined by a pathologist to confirm the presence of neuroblastoma cells. Specific characteristics, including the appearance and behavior of the cells, will help determine the type and grade of the tumor.

6. Staging:

Once a diagnosis is made, staging tests are performed to determine the extent of the disease. This typically involves:

• Additional imaging studies to assess distant spread.
• Evaluations to determine if there are metastases present in the bones, lymph nodes, liver, or other organs.

Conclusion:

The diagnosis of neuroblastoma involves a multifaceted approach, including clinical evaluation, imaging studies, laboratory tests, and histological examination of tissue samples. Early diagnosis is key to improving treatment outcomes; therefore, if neuroblastoma is suspected based on symptoms and initial evaluations, it is essential to proceed with further testing and work closely with pediatric oncologists to determine the best course of action for the child.

What is the treatment for neuroblastoma?

The treatment for neuroblastoma varies based on several factors, including the age of the child, the stage of the disease, the tumor’s location, and whether it has spread (metastasized). A multidisciplinary approach is often used, and treatment may involve a combination of therapies. Here is an overview of the primary treatment options for neuroblastoma:

1. Surgery:

• Tumor Removal: Surgical intervention aims to remove as much of the tumor as possible.
• Localized Neuroblastoma: If the tumor is localized and completely resectable (able to be surgically removed), surgery may be the first line of treatment.
• Advanced Disease: In cases where the tumor is large or has spread, surgery may be performed after other treatments (like chemotherapy) to shrink the tumor.

2. Chemotherapy:

• Preoperative (Neoadjuvant) Chemotherapy: This may be administered before surgery to shrink the tumor, making it easier to remove.
• Postoperative (Adjuvant) Chemotherapy: After surgery, chemotherapy is typically used to eliminate any remaining cancer cells and reduce the risk of recurrence.
• Chemotherapy Regimens: The specific drugs and regimens depend on the risk classification of the neuroblastoma and may include a combination of agents such as cyclophosphamide, doxorubicin, and cisplatin, among others.

3. Radiation Therapy:

• Localized Radiation: Radiation therapy may be used after surgery to target any remaining tumor cells, particularly if the tumor is in a location that makes complete surgical removal difficult.
• Palliative Radiation: In advanced cases or if the cancer has spread to the bones or other areas, radiation may be used to relieve symptoms and control disease progression.

4. Stem Cell Transplant:

• High-Dose Chemotherapy with Stem Cell Rescue: For high-risk neuroblastoma cases, high doses of chemotherapy may be given followed by a stem cell transplant. This involves harvesting stem cells from the child’s blood or bone marrow before chemotherapy and reinfusing them afterward to help recover the bone marrow.

5. Immunotherapy:

• Monoclonal Antibodies: Targeted therapies, such as dinutuximab (Unituxin), may be used in combination with other treatments to enhance the immune response against neuroblastoma cells. These therapies specifically target neuroblastoma cells and help to destroy them while sparing normal cells.
• Chimeric Antigen Receptor (CAR) T-cell Therapy: Research is ongoing into using CAR T-cell therapy, where a child’s own T-cells are modified to better recognize and kill cancer cells.

6. Clinical Trials:

• Experimental Treatments: Many children with neuroblastoma may be eligible for clinical trials exploring new treatment options. This could include innovative drugs, combinations of therapies, or novel approaches to treatment.

Conclusion:

The treatment for neuroblastoma is complex and depends on a range of factors, including the child’s age and overall health, the stage of the cancer, and the specific characteristics of the tumor. Effective management typically involves a combination of surgery, chemotherapy, radiation therapy, immunotherapy, and possibly stem cell transplantation. The treatment plan is developed by a multidisciplinary team of pediatric oncologists, surgeons, radiologists, and other specialists who work collaboratively to provide the best possible outcome for the child. Early diagnosis and a comprehensive treatment strategy are crucial for improving survival rates and quality of life in children with neuroblastoma.

What is the survival rate for neuroblastoma?

The survival rates for neuroblastoma vary significantly depending on several factors, including age at diagnosis, tumor stage, and tumor biology. Generally, the overall five-year survival rate for neuroblastoma is around 80% for children diagnosed at an early stage. However, for high-risk neuroblastoma, the survival rate drops significantly, often falling below 50%. Early detection and treatment are crucial for improving outcomes.