Neuroblastoma is a cancer that develops from immature nerve cells, most often appearing in infants and young children. It accounts for 8 to 10 percent of all childhood cancers, making it the most common solid tumor in children outside the brain. The median age at diagnosis is 17 to 18 months, and while some forms are aggressive, others can actually shrink and disappear on their own without treatment.
Where Neuroblastoma Comes From
During early development in the womb, a band of cells called the neural crest migrates throughout the embryo and matures into various structures, including nerve cells of the sympathetic nervous system and hormone-producing cells in the adrenal glands. Neuroblastoma arises when some of these migrating cells fail to mature properly. Instead of becoming functioning nerve or adrenal cells, they keep dividing in their immature state and form a tumor.
Because neural crest cells travel to so many parts of the body during development, the tumor can appear in several locations. The most common site is the adrenal glands, which sit on top of the kidneys. But neuroblastoma can also develop along the spine, in the chest, pelvis, or neck, essentially anywhere the sympathetic nervous system reaches.
Signs and Symptoms
The symptoms depend heavily on where the tumor grows. Since the adrenal glands are the most frequent site, many children first present with a firm mass in the abdomen that a parent or doctor can feel. Abdominal tumors can also cause swelling, pain, or changes in bowel habits as the mass presses on nearby organs.
Tumors in the chest or neck can cause different signs. A growth near the upper spine or neck may compress certain nerves and produce Horner syndrome, a combination of a drooping eyelid, a smaller pupil, and decreased sweating on one side of the face. Some children develop bone pain, limping, or bruising around the eyes if the cancer has spread. Because the tumor cells often produce excess catecholamines (the same family of chemicals as adrenaline), urine tests can detect elevated levels of two breakdown products in roughly 90 to 95 percent of cases, making this a useful early diagnostic tool.
How Doctors Determine Risk
One of the most distinctive things about neuroblastoma is how differently it can behave from one child to the next. A tumor in one infant may vanish without treatment, while an identical-looking tumor in another child proves aggressive and resistant to therapy. To address this, doctors classify each case into risk categories: low, intermediate, or high.
Several factors determine a child’s risk group. Age matters: children diagnosed before 18 months generally do better. The extent of the tumor is assessed using a staging system that ranges from L1 (a localized tumor not involving vital structures) to M (cancer that has spread to distant sites). Tumor biology also plays a major role. The single most important genetic marker is amplification of a gene called MYCN, found in about 25 percent of cases. When the tumor carries extra copies of this gene, it correlates strongly with aggressive disease and poorer outcomes. Other factors include the tumor’s appearance under a microscope and specific chromosome changes.
The Special Case of Stage MS
One of the most remarkable phenomena in all of cancer medicine occurs in a subset of neuroblastoma patients younger than 18 months. These children have a small primary tumor that has spread to the liver, skin, or bone marrow, but not to the bones themselves. First described in 1971 and now designated Stage MS, this pattern would seem alarming, yet these tumors have an extraordinary capacity to simply regress on their own.
Researchers believe this spontaneous regression relates to the biology of the tumor cells themselves. Stage MS tumors tend to have low activity of telomerase, the enzyme that maintains the protective caps on chromosomes. Without that maintenance, the tumor cells essentially age themselves out of existence. Another proposed mechanism involves a receptor on the tumor cell surface that, when deprived of its growth signal, triggers the cells to self-destruct. The practical result is that many of these children need only careful monitoring rather than aggressive treatment, and their outcomes are excellent.
Treatment for High-Risk Disease
Children with high-risk neuroblastoma face one of the most intensive treatment regimens in pediatric oncology, typically lasting about 18 months and divided into three phases.
The first phase, induction, involves five to eight cycles of intensive chemotherapy designed to shrink the tumor. Surgical removal of the primary tumor usually happens partway through this phase, after the chemotherapy has reduced its size enough to make surgery safer. The second phase, consolidation, uses very high doses of chemotherapy that would normally destroy the bone marrow. Stem cells collected from the child earlier in treatment are then transplanted back to rebuild blood cell production. Radiation therapy to the original tumor site is also given during this phase.
The third phase targets any remaining cancer cells that may have survived. This is where immunotherapy comes in. A treatment that targets a molecule called GD2 on the surface of neuroblastoma cells has become a standard part of care after a clinical trial showed it significantly improved outcomes. Children who received this antibody-based immunotherapy alongside other agents had a 66 percent event-free survival rate, compared to 46 percent for those who received standard maintenance therapy alone. This immunotherapy, combined with a vitamin A derivative that encourages residual neuroblastoma cells to mature into harmless cells, now forms the backbone of post-transplant care.
Survival by Risk Group
Outcomes vary dramatically based on risk classification. Children with low-risk neuroblastoma have survival rates above 95 percent, and many are treated with surgery alone or even observation. Intermediate-risk patients also do well, with survival rates generally above 90 percent using moderate chemotherapy and surgery.
High-risk disease remains the major challenge. Even with the full arsenal of chemotherapy, surgery, transplant, radiation, and immunotherapy, long-term survival for high-risk patients hovers around 50 to 60 percent. The addition of immunotherapy over the past decade has been the single biggest improvement in these numbers, but relapse remains common and is difficult to treat.
Long-Term Effects for Survivors
Children who survive neuroblastoma, particularly those treated for high-risk disease, often face lasting health effects from the intensity of their treatment. Hearing loss is one of the most common, detected in 62 percent of advanced-stage survivors in one study, primarily caused by the platinum-based chemotherapy drugs used during induction. Radiation to areas near the spine or other bones can cause localized bone thinning, curvature of the spine, and growth problems. Some survivors develop hormone deficiencies, including low growth hormone or disrupted puberty, that require ongoing management.
There is also an increased rate of second cancers compared to the general population, a consequence of the DNA-damaging therapies used to treat the original disease. For these reasons, neuroblastoma survivors benefit from long-term follow-up programs that monitor hearing, growth, hormonal function, heart health, and cancer screening well into adulthood.