What Is Neuroblastoma?
Neuroblastoma is a rare childhood cancer that begins in very early forms of nerve cells called neuroblasts. These immature cells are a normal part of fetal development, but in neuroblastoma, they fail to mature properly. Instead, they multiply uncontrollably and form solid tumors. This cancer is known for its wide range of behaviors, from disappearing on its own to spreading aggressively.
Origin in Early Nerve Cells
This cancer arises from neuroblasts, which are leftover cells from a baby’s development in the womb. Normally, these cells are destined to mature into the sympathetic nervous system—the network that manages the body's "fight or flight" responses by controlling functions like heart rate, blood pressure, and digestion. In neuroblastoma, a developmental error prevents this maturation, causing the cells to grow into a tumor instead.
Common Tumor Locations
Because neuroblasts are part of the sympathetic nervous system, tumors can develop anywhere along this network. The most common site is the adrenal glands, which are small glands located on top of the kidneys. However, tumors can also form in nerve tissue along the spine in the neck, chest, abdomen, or pelvis. The tumor's location often determines the specific signs and symptoms a child may experience.
A Uniquely Unpredictable Cancer
Neuroblastoma is remarkable for its varied behavior. In some infants, the tumor may mature into harmless tissue or even disappear without any treatment, a process known as spontaneous regression. In other children, the disease can be extremely aggressive, growing quickly and spreading to other parts of the body like the bone marrow, bones, liver, and skin. This unpredictability is a key challenge for doctors in determining the best course of treatment.
How Neuroblastoma is Staged
Once neuroblastoma is diagnosed, doctors perform staging to determine the extent of the cancer—how large the tumor is and whether it has spread. Staging is a critical step that provides a roadmap for the medical team to create the most effective treatment plan. Two primary systems are used to stage neuroblastoma.
The International Neuroblastoma Staging System (INSS)
The INSS classifies the tumor after surgery has been performed. Its stages are based on how much of the tumor was surgically removed and whether it has crossed the midline of the body (an imaginary line dividing the body into left and right). The final INSS stage is only confirmed after the initial operation, as it depends on the surgical outcome.
The International Neuroblastoma Risk Group Staging System (INRGSS)
A more modern approach, the INRGSS stages the cancer before any treatment begins, using imaging tests like CT or MRI scans. This system looks for "Image-Defined Risk Factors" (IDRFs)—signs on a scan that suggest the tumor is wrapped around major blood vessels or has invaded nearby organs. This pre-treatment staging helps doctors predict surgical risks upfront and decide if chemotherapy is needed first to shrink the tumor, making a future operation safer and more effective.
The INSS Stages Explained
The INSS stages provide a detailed picture of the tumor's extent based on surgical findings.
Stage 1
This is the most favorable stage. It describes a localized tumor that was completely removed during surgery. To be classified as Stage 1, doctors must confirm that no cancer cells were left behind and that nearby lymph nodes are cancer-free. Children with Stage 1 neuroblastoma have an excellent prognosis and may not need any further treatment.
Stage 2A and 2B
This stage also describes a localized tumor, but one that could not be completely removed with surgery alone.
- Stage 2A: The tumor was not fully removed, but the nearby lymph nodes are free of cancer.
- Stage 2B: The tumor was not fully removed, and cancer cells were also found in lymph nodes on the same side of the body as the tumor. Treatment for Stage 2 often includes chemotherapy to eliminate the remaining cancer cells.
Stage 3
This stage describes a large tumor that could not be completely removed and has grown across the body’s midline. For example, a tumor starting near the left kidney may have grown to involve areas on the right side. In other cases, the primary tumor is on one side, but cancer is found in lymph nodes on the opposite side. Treatment for Stage 3 typically starts with chemotherapy to shrink the tumor before surgery is attempted.
Stage 4
Stage 4 means the cancer has metastasized, or spread, to distant parts of the body. Common sites of spread include distant lymph nodes, bones, bone marrow, the liver, and skin. Because the disease is widespread, treatment must be systemic, targeting cancer cells throughout the entire body. This involves an intensive combination of therapies, such as high-dose chemotherapy, surgery, radiation, and immunotherapy.
Stage 4S (Special)
This unique category is reserved for infants under 18 months old. These babies have a small, localized primary tumor (similar to Stage 1 or 2), but the cancer has also spread to the liver, skin, and/or a small amount in the bone marrow. Despite being metastatic, the tumors in many Stage 4S infants will spontaneously regress—maturing into harmless tissue or disappearing on their own with little or no treatment. Doctors monitor these children closely, intervening only if the tumors cause life-threatening problems.
Beyond Staging: How Stage Determines a Patient's Risk Group
A tumor's stage is just one piece of the puzzle. To create the best treatment plan, doctors combine the stage with the child's age and the tumor's biological features, including its genetics. This complete picture places each child into a risk group—low, intermediate, or high—which ultimately guides the intensity of therapy.
Low-Risk Group
This group has the best prognosis. It typically includes children with Stage 1 or 2 tumors with "favorable biology" and infants with Stage 4S disease. The goal is to cure the cancer with the least amount of treatment to minimize long-term side effects. For some, surgery alone is enough, while others may only require careful observation as the tumor regresses on its own.
Intermediate-Risk Group
This category often includes children with larger, localized tumors (like Stage 3) or those with some unfavorable biological features. The cancer is more extensive than in the low-risk group but not as widespread or aggressive as in the high-risk group. Treatment is more intensive, usually involving both chemotherapy and surgery to achieve a cure while balancing treatment effectiveness against long-term health risks.
High-Risk Group
This group faces the most difficult-to-treat cancers. It includes most children over 18 months with Stage 4 metastatic disease. Additionally, any patient whose tumor has a specific genetic change called MYCN amplification is automatically classified as high-risk, regardless of their age or stage. Treatment for this group is the most complex and aggressive, involving multiple phases of high-dose chemotherapy, surgery, radiation, stem cell transplant, and immunotherapy.
