#164: Notes on Neuroblastoma

January 14, 2026 | By Sam Masur

Audio

Join us this week for a fantastic discussion about neuroblastoma courtesy of our guest, Dr. Brittany Greene of Seattle Children’s Hospital. We discuss common presenting symptoms, work-up, and the nuance of stage-specific treatment! 

Neuroblastoma Pearls

1. Neuroblastoma can present at any age, but peak diagnosis is usually between 18 months and 3 years of age. 
2. Age at diagnosis (and disease extent) are crucial indicators that drive treatment, which can range from watchful waiting to intensive chemotherapy. 
3. Keep neuroblastoma on your differential in a patient with appropriate symptoms, but routine surveillance screening has not proven to improve patient care/outcomes. 

Neuroblastoma Notes 

Pathophysiology & Presentation

Neuroblastoma is a common pediatric embryonal cancer that originates from neuroblasts. These cells arise from the neural crest and are present during fetal development, and are located throughout the sympathetic nervous system. 

Neuroblastoma can have a wide variety of presentations, depending on the location(s) of the tumor. The most common point of origin in neuroblastoma is the adrenal glands, so downstream effects of abdominal tumors are most often seen. This can include malaise, poor intake, and sometimes refractory constipation. Abdominal distention can sometimes be noted by family, but this is not common (as the tumors are often slow-growing). Unlike other embryonal abdominal tumors like Wilm’s tumors, neuroblastomas often cross the midline of the abdomen. Additionally, neuroblastoma can present as a paraspinal or thoracic mass. In that case, respiratory symptoms or Horner’s syndrome may be more likely. Lastly, if it’s paraspinal in origin, neuroblastoma may present with sudden neurological deficits. Sometimes, this becomes an emergency if there is a concern for spinal cord compression and/or acute paralysis. 

Periorbital bruising (with no known inciting injury) should raise suspicion for neuroblastoma, as metastatic disease to the orbits can present with periorbital bruising (aka, raccoon eyes). It’s also common for neuroblastoma to invade the bone marrow, thus causing diffuse symptoms such as refusal to walk, fevers, bruising/bleeding. As the neuroblastoma cells invade the marrow, the patient’s ability to make their own cells begins to diminish. 

There are two rare, but pathognomonic presentations for neuroblastoma that are important to remember. 

• In newborns specifically, neuroblastoma can present as a purplish rash (nicknamed the “blueberry muffin rash”. This is caused by the neuroblastoma cells metastasizing to the skin.
• Neuroblastoma can trigger a paraneoplastic syndrome called opsoclonus-myoclonus syndrome (OMS). In children who present with new-onset OMS, about half are found to have neuroblastoma. Symptoms include ataxia, myoclonus, opsoclonus (rapid eye movements in all directions), and irritability. Interestingly, the cancer triggering the syndrome is often a lower-risk disease, but these patients often require additional treatment such as steroids, IVIG, Rituximab, etc. to assist with the OMS symptoms- which can be quite disabling. 

Workup & Diagnosis

If there is a concern for potential neuroblastoma, the patient should be referred to the pediatric emergency department for additional work-up and management. Abdominal imaging is likely to be obtained, such as a CT of the abdomen/pelvis. Imaging of the chest may be obtained as well, if there is a concern for thoracic tumor or to evaluate metastasis from an abdominal tumor. Patients will often have a host of labs obtained, such as CBC, LDH, uric acid, and catecholamines. Catecholamines can be indicative of neuroblastoma, as there will be elevations of VMA or HVA. These can be obtained via blood serum or urine – this may be institution-specific. If it’s not clear where the abdominal tumor is arising from, an AFP and/or beta HCG can help distinguish. Often, patients are admitted for additional inpatient work-up (see below). 

After initial stability and diagnosis, a patient will often undergo an MIBG scan. It’s similar to a PET scan, in that a radiolabeled agent will be injected into the patient’s body. From there, the injected nucleotide is picked up by neuroblastoma cells, thus allowing the medical team to determine the extent of oncologic disease. Furthermore, bilateral bone marrow biopsies will be obtained. Unlike a disease like leukemia, neuroblastoma has a more “patchy” appearance in the marrow. Because of this, bone marrow biopsies are bilateral. Lastly, a biopsy of the tumor is obtained. This is the last step in confirming the histology, and also is helpful in evaluating molecular markers for staging/prognosis and management. This “order of operations” can change depending on how patients present and their stability. 

Ages & Stages

Neuroblastomas have a broad age distribution (from prenatal diagnosis through adolescents/young adults), but the majority of patients are diagnosed as toddlers/preschool age (think 18months-3 years). Interestingly, neuroblastomas can behave differently depending on the age of the patient! 

• In infants (<1 year of age), often the initial plan of care is watchful waiting. The tumor can spontaneously regress! Because of how advanced prenatal imaging has become, sometimes adrenal masses are found prior to delivery. In these cases, serial ultrasound and catecholamine monitoring is sufficient. If the tumor continues to grow in size, they may ultimately warrant surgical intervention. 
• Conversely, adolescents who present with neuroblastoma often have a completely different “behavior” of their tumor, in that it is slow-growing and sometimes less responsive to treatment. 

Besides age at diagnosis, staging neuroblastoma can be dependent on metastasis (local versus diffuse), as well as molecular factors. However, age is often the most important marker. 

Treatment

Treatment for neuroblastoma can vary based on age and stage. Dr. Greene points out that, oftentimes, parents/guardians will worry that they have “missed” something by not bringing their child in sooner (especially if they have metastatic disease). It’s important to note that children with neuroblastoma often present with metastases, and this doesn’t necessarily impact their outcome more than age and molecular biology. Children diagnosed with high-risk neuroblastoma (which is about half of patients), go through an intensive process. This includes induction chemotherapy, surgical resection of the primary tumor, high dose chemotherapy with autologous stem cell transplant (twice!), radiation therapy, and immunotherapy. Surgical resection of these tumors can get tricky, because the tumors are often enveloping abdominal vasculature. 

Intermediate risk may include chemotherapy and surgical resection (albeit not as commonly). Low risk neuroblastoma is often watchful waiting with surgical intervention as needed. Low risk patients do not routinely receive chemotherapy. 

Survivorship & Beyond

After initial treatment, disease surveillance will look different depending on the age of the patient, stage at diagnosis, etc. For the first 1-2 years, the oncology team is closely monitoring patients due to the risk of relapse. This evaluation may include abdominal imaging and labwork. As patients are farther out from their treatment completion date, surveillance studies will be spaced out accordingly. Overall survival is the number of patients who are alive at a certain time marker following diagnosis. Event-free survival is more nuanced, in that it would exclude patients who may have a relapse or other negative impact of their disease (but are alive). 

High-risk neuroblastoma has, historically, held a poor prognosis- but new treatments continue to increase survivorship. 

Like many pediatric cancers, there are outcome disparities depending on a patient’s race and/or socioeconomic status. Neuroblastoma is unique in that most of the treatment is inpatient, so it’s a “controlled” environment. Even then, however, Black and Hispanic children with high risk neuroblastoma have worse outcomes. Additionally, lower socioeconomic status is associated with decreased survival in children with high risk neuroblastoma. 

Screening

Is there a place for universal catecholamine screening to diagnose neuroblastoma earlier? Unfortunately, no. Studies have shown that mass screening in this manner does not improve outcomes, and may lead to overdiagnosis and associated harm. 

Links

Dancing Eyes-Opsoclonus Myoclonus Ataxia Syndrome in Neuroblastoma

Opsoclonus Myoclonus Syndrome: Symptoms, Challenges, and Treatment Options

Goal

Listeners will explain the basic pathophysiology, diagnosis, and management of neuroblastoma to improve both diagnosis and emergent treatment awareness. 

Learning Objectives

After listening to this episode listeners will…  

1. Recall the basic pathophysiology of neuroblastoma.
2. Be familiar with common symptoms that warrant further work-up.
3. Recognize the importance of recognizing rare, but pathognomic presentations such as blueberry muffin rash and opsoclonus-myoclonus syndrome. 
4. Describe the typical inpatient diagnostic work-up. 
5. Learn about treatment modalities and staging. 

Disclosures

Dr Greene reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

Wells E, Greene B, Berk J, Chiu C, Masur S. “#164: Notes on Neuroblastoma”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ January 14, 2026.