Topics in 10: Neuroblastoma

Published: 2019-09-12

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Inside this episode

Kai, the Library's AI content creator, listened to this episode and mapped who's speaking, the chapters, key claims, and cases. Every item links to the exact moment in the recording.

AI-enriched

Who's speaking

Ray Hanke — host
Speaker 2 — host
Daniel von Allman — guest

Chapters

0:00Introduction and Clinical Presentation — Overview of neuroblastoma epidemiology and typical presentations including prenatal detection, abdominal mass, and metastatic symptoms.
1:32Diagnostic Workup and Staging — Diagnostic approach using catecholamines, cross-sectional imaging, MIBG scan, and the INRGSS pre-biopsy staging system.
3:53Surgical Approach and Biopsy — Surgical decision-making for resectable versus unresectable tumors, biopsy techniques, and biologic risk markers.
5:45Risk Stratification and Treatment — Risk-based treatment protocols for very low, low, intermediate, and high-risk neuroblastoma, including observation, chemotherapy, surgery, and multimodal therapy.
9:00Clinical Pearls Summary — Recap of key clinical points and treatment algorithms.

Key claims

0:00Neuroblastoma is the most common extracranial solid tumor in children — Ray Hanke
0:00The majority of neuroblastoma cases occur in children less than a year old — Ray Hanke
0:41Younger patients are often picked up prenatally on ultrasound or as a solid abdominal mass in two- or three-year-olds — Daniel von Allman
0:41Patients with metastatic disease may present with bony pain or neurologic symptoms from cord compression — Daniel von Allman
1:07Catecholamines (urine or serum) are one of the most diagnostic laboratory tests for neuroblastoma — Daniel von Allman
1:39Cross-sectional imaging (CT or MRI) is obtained after initial ultrasound and laboratory workup — Daniel von Allman
1:39MIBG study is helpful for confirming neuroblastoma diagnosis and demonstrating metastatic disease — Daniel von Allman
2:20About 10% of neuroblastomas are MIBG negative — Daniel von Allman
2:20Some centers obtain a PET scan for MIBG-negative cases to look for tumor uptake and metastatic disease — Daniel von Allman
2:45The INRGSS staging system allows stage assignment before any invasive procedure — Daniel von Allman
2:45Localized tumors without image-defined risk factors are categorized as L1 — Daniel von Allman
2:45Localized tumors with image-defined risk factors (encasing nerves or vessels) are L2 — Daniel von Allman
2:45Tumors with metastatic disease are categorized as M — Daniel von Allman
2:45MS category is for children less than 18 months with metastases to bone marrow or skin — Daniel von Allman
3:36The INRGSS was created to allow studies from different centers and countries to be compared based on pre-surgical staging — Daniel von Allman
3:36The prior staging system required tissue diagnosis before assigning a stage — Daniel von Allman
4:06A patient with a resectable adrenal mass and positive MIBG without metastases can be treated with primary resection via laparotomy or laparoscopy — Daniel von Allman
4:44For large central abdominal tumors that encase major vasculature, only tissue for diagnosis is needed via open biopsy, laparoscopic biopsy, or core needle biopsy — Daniel von Allman
5:14NMIC status is the most important biologic risk determinant from biopsy tissue — Daniel von Allman
5:141P and 11Q deletions should be assessed in biopsy tissue along with Shimada histology — Daniel von Allman
5:45Neuroblastoma risk categories are very low risk, low risk, intermediate risk, or high risk — Daniel von Allman
5:45Risk distribution is approximately 50-50 between low risk categories and high risk, with a smaller percentage intermediate risk — Daniel von Allman
6:06NMIC amplification and age greater than 18 months are the most important prognostic determinants for neuroblastoma — Daniel von Allman
6:06High-risk patients receive aggressive chemotherapy including peripheral stem cell transplant times 2, aggressive surgery with >90% resection goal, radiation, immunotherapy, and potentially retinoic acid therapy — Daniel von Allman
6:51Intermediate risk tumors receive varying cycles of chemotherapy based on biologic risk factors — Daniel von Allman
6:51For intermediate risk tumors, the surgical goal is at least 50% response from initial primary tumor volume combining neoadjuvant chemotherapy and surgical resection — Daniel von Allman
7:22Low risk patients, depending on age and diagnosis timing, could be followed with observation alone — Daniel von Allman
7:22A Children's Oncology Group study led by Jed Nocturne showed patients less than six months with prenatally or early postnatally diagnosed localized mass can be observed with expectation that most will avoid surgery — Daniel von Allman
7:55Patients with metastatic disease typically receive four or five cycles of neoadjuvant chemotherapy and are then reassessed — Daniel von Allman
7:55If metastatic disease is responding to chemotherapy, the primary tumor site should be resected with attempted >90% resection — Daniel von Allman
7:55If metastatic disease is progressing on chemotherapy, surgery is not indicated — Daniel von Allman
7:55MS disease is for patients less than 18 months with primary site and metastases to liver, skin, or bone marrow (specifically not cortical bone) — Daniel von Allman
7:55MS disease patients can be managed with simple observation; treatment is only elected if they progress or develop complications like respiratory issues from enlarging liver mass — Daniel von Allman
8:55Skin lesions in MS disease can be biopsied to provide diagnosis — Daniel von Allman

This episode was analyzed and enriched by Kai, the Library's AI content creator. Every item links to the moment it comes from — click a timestamp to listen in context.

Neuroblastoma: Risk-Stratified Management of Childhood's Most Common Solid Tumor

The episode's main topic retold as a plain-language walkthrough — what it is, why it matters, and what the speakers concluded. Written by Kai from the episode transcript and reviewed before publishing.

For the care team · Explainer · AI-written, human-reviewed

Why This Exists as a Distinct Discipline

Neuroblastoma occupies a unique position in pediatric oncology — it is the most common extracranial solid tumor in children, yet its behavior spans an extraordinary clinical range 0:00. The same histologic diagnosis can present as a prenatal adrenal mass that regresses without intervention or as widely metastatic disease requiring stem cell transplant. This biological heterogeneity, coupled with the tumor's origin from sympathetic nervous system tissue and its propensity to encase major vessels, demands subspecialized surgical and oncologic judgment that general pediatrics cannot provide.

The Core Clinical Problem

Neuroblastoma arises from neural crest cells and most commonly presents in infancy — the majority of cases occur in children less than a year old 0:00. Younger patients are often identified prenatally on ultrasound or present with a palpable abdominal mass in the first few years of life 0:41. Patients with metastatic disease may present with bony pain or neurologic symptoms from cord compression 0:41. The central challenge is not diagnosis — elevated catecholamines (urine or serum) are highly diagnostic 1:07, and MIBG scanning confirms the tumor and maps metastases in 90% of cases 1:39 2:20 — but rather determining which tumors require aggressive multimodal therapy and which can be observed to spontaneous regression.

How the Approach Works

The modern management framework rests on pre-surgical staging and biologic risk stratification. After initial ultrasound and laboratory workup, cross-sectional imaging (CT or MRI) defines the tumor's relationship to surrounding structures 1:39. An MIBG study follows to confirm diagnosis and identify metastatic disease 1:39; for the 10% of MIBG-negative tumors, some centers obtain a PET scan 2:20 2:20.

The International Neuroblastoma Risk Group Staging System (INRGSS) allows stage assignment before any invasive procedure 2:45. This was specifically created to allow studies from different centers and countries to be compared based on pre-surgical staging, replacing a prior system that required tissue diagnosis first 3:36 3:36. Localized tumors without image-defined risk factors are L1; those with risk factors — encasing nerves or vessels — are L2 2:45 2:45. Metastatic disease is M 2:45. A special category, MS, applies to children less than 18 months with metastases to bone marrow or skin but not cortical bone 2:45 7:55.

Surgical strategy diverges at this point. A patient with a resectable adrenal mass, positive MIBG, and no metastases can proceed directly to resection via laparotomy or laparoscopy 4:06. For large central abdominal tumors that encase major vasculature, only tissue for diagnosis is needed — obtained via open biopsy, laparoscopic biopsy, or core needle biopsy 4:44.

What matters most in that biopsy is NMIC status, the single most important biologic risk determinant 5:14. The tissue should also be assessed for 1P and 11Q deletions and Shimada histology 5:14. These markers, combined with age, assign patients to very low, low, intermediate, or high risk categories 5:45. The distribution is roughly 50-50 between low-risk categories and high-risk, with a smaller percentage intermediate 5:45. NMIC amplification and age greater than 18 months are the most important prognostic determinants 6:06.

Treatment intensity scales with risk. High-risk patients receive aggressive chemotherapy including peripheral stem cell transplant times two, aggressive surgery targeting greater than 90% resection, radiation, immunotherapy, and potentially retinoic acid therapy 6:06. Intermediate-risk tumors receive varying cycles of chemotherapy based on biologic factors; the surgical goal is at least 50% response from initial primary tumor volume, combining neoadjuvant chemotherapy and surgical resection 6:51 6:51. Low-risk patients, depending on age and diagnosis timing, can be followed with observation alone 7:22. A Children's Oncology Group study demonstrated that patients less than six months with prenatally or early postnatally diagnosed localized mass can be observed, with the expectation that most will avoid surgery 7:22.

For metastatic disease, patients typically receive four or five cycles of neoadjuvant chemotherapy and are then reassessed 7:55. If metastatic disease is responding, the primary tumor site should be resected with attempted greater than 90% resection 7:55. If metastatic disease is progressing, surgery is not indicated 7:55.

The MS category deserves special attention. These are patients less than 18 months with a primary site and metastases specifically to liver, skin, or bone marrow — not cortical bone 7:55. These patients can be managed with simple observation; treatment is only elected if they progress or develop complications like respiratory issues from an enlarging liver mass 7:55. Skin lesions can be biopsied to provide diagnosis 8:55.

Where Practice Is Contested

The discussants did not address areas of genuine clinical controversy, though the existence of multiple risk-stratification schemas and the evolution from older staging systems to INRGSS suggests this remains an area of active refinement.

When to Involve This Team

Any child with a solid abdominal mass and elevated catecholamines requires immediate pediatric oncology and surgical oncology consultation. Prenatal adrenal masses identified on ultrasound should be referred for postnatal evaluation. Do not delay referral to obtain tissue yourself — the biopsy strategy depends on resectability, and that judgment requires subspecialty imaging interpretation and multidisciplinary planning.

Takeaways from this story

NMIC amplification and age >18 months are the most important prognostic factors driving risk stratification and treatment intensity.
MS disease (infants <18mo with mets to marrow/skin, not bone) can be observed — most regress without treatment.
INRGSS staging happens before biopsy using imaging alone, enabling pre-surgical treatment planning and study comparison.
Surgical goals vary by risk: low-risk may avoid surgery entirely, intermediate aims for 50% reduction, high-risk targets >90% resection.
For metastatic disease, surgery is only indicated if metastases respond to chemotherapy — progressing mets contraindicate resection.

Topic overview

This discussion covers the clinical approach to neuroblastoma, the most common extracranial solid tumor in children. Dr. Daniel von Allman, Surgeon-in-Chief at Cincinnati Children's Hospital, describes presentation patterns (prenatal detection, abdominal mass, metastatic symptoms), diagnostic workup (catecholamines, cross-sectional imaging, MIBG scan), the INRGSS pre-biopsy staging system, and tissue biopsy requirements for biologic risk stratification (NMIC status, 1P/11Q deletions, Shimada histology). Treatment is risk-stratified: low-risk tumors may be observed, intermediate-risk receive chemotherapy with 50% tumor reduction goals, and high-risk disease requires aggressive multimodal therapy including chemotherapy, >90% surgical resection, radiation, stem cell transplant, and immunotherapy. The MS category for infants under 18 months with specific metastatic patterns often permits observation alone.

Key takeaways

INRGSS staging enables pre-biopsy risk stratification: L1 (no vascular encasement), L2 (encases vessels/nerves), M (mets), MS (<18mo, marrow/skin). (2:45)
NMIC amplification + age >18mo are top prognostic factors; high-risk disease demands >90% resection, transplant, radiation, immunotherapy. (6:06)
Intermediate-risk goal: ≥50% volume reduction via chemo + surgery. Low-risk infants (<6mo, localized) may be observed without resection. (6:51)
MS disease (age <18mo, liver/skin/marrow mets, no cortical bone) often regresses spontaneously; treat only if complications arise. (7:55)
~10% of neuroblastomas are MIBG-negative; PET scan can identify uptake and metastases in these cases. (2:20)

Keywords

neuroblastoma metastatic disease cord compression MS disease ultrasound CT scan MRI MIBG scan PET scan laparotomy laparoscopy open biopsy laparoscopic biopsy core needle biopsy peripheral stem cell transplant

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Transcript

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It's hard to stay on top of the rapidly changing literature in the limited hours we have in a day. We just released the full audio chapter covering everything you need to know about neuroblastoma. As promised, here's neuroblastoma in 10 for those of you who want the cliff notes. Let's get to it. Neuroblastoma is the most common extracranial solid tumor in children, with the majority occurring in children less than a year old. Dr. Daniel von Allman, Surgeon-in-Chief at Cincinnati Children's Hospital, joins us to give us the essentials. How do these patients typically present? So in the younger patients, they're oftentimes picked up either prenatally on ultrasound, or in younger kids, say two-year-old or three-year-old, it might be picked up as a solid abdominal mass. Occasionally, when they have metastatic disease, they'll present with either bony pain or potentially neurologic symptoms from cord compression. Okay, so if a child presents, let's say, with an abdominal mass, how do you usually work them up? So oftentimes, when a child presents to the emergency room, they may get an ultrasound, which will demonstrate a solid mass in the abdomen. Those kids then will get a laboratory workup, and as part of the differential diagnosis, when you consider neuroblastoma, it's important to get catecholamines, either urine or serum catecholamines, as one of the most diagnostic laboratory tests that we use for this tumor. Okay, so they come in, you have suspicion for neuroblastoma, you get the blood work and the urine test. Now what? Most kids would then get a cross-sectional imaging study, either a CT scan or an MRI. If those studies suggest a neuroblastoma, that is either a central abdominal mass or adrenal mass, rather than, for example, a kidney mass, then the next test would be a nuclear medicine study, typically an MIBG study. The MIBG study is helpful for confirming the diagnosis of neuroblastoma and also can demonstrate a metastatic disease. So now you have your blood work, your cross-sectional imaging, and your MIBG scan. Is that 100% accurate, the MIBG scan? The scan, an MIBG is not 100% accurate. About 10% of neuroblastomas are MIBG negative. Some centers, including ours, would get a PET scan looking for, again, tumor uptake as well as potential metastatic disease. All right, so now you have all of your imaging and blood work and your MIBG scan. Can you stage at this point? So based on the most recent iteration of the neuroblastoma staging system, the INRGSS, it is possible to assign a stage before any invasive procedure is performed. So tumors that are localized are categorized as L1. If they're localized but have what are called image-defined risk factors, that is, they may encase nerves or vessels, and there's a whole long list of image-defined risk factors for each body cavity, then they would be L2. If they have metastatic disease, they're M. And then there's the special category of MS for children that are less than 18 months of age who have metastases to either the bone marrow or the skin. Okay, so this pre-biopsy staging system is helpful because you don't always necessarily proceed in the same direction based on some of these stages. So this was specifically created to allow studies from different centers in different countries to be compared based on the pre-surgical staging of the patient. The prior staging system required tissue diagnosis before assigning a stage. Okay, let's take the patient that has an adrenal mass on the right side and a positive MIBG scan but no evidence of metastases on the MIBG scan. How do you proceed on that patient? So that child is potentially could be treated with a primary resection of the mass. If there's no evidence of other tumor, the mass looks resectable. I would treat that patient with a laparotomy and resection. Some people would approach that with laparoscopy depending on the size of the tumor. And your job at that point is to go in and remove the tumor and take any obvious loop nodes in the area? Correct. Okay. Let's take another situation that it is a very large mass, maybe emanating from the adrenal, but it involves a lot of the vascular supply in the area. Now what? Yeah, typically those are central abdominal types of tumors that encase the aorta, the cava, other major vasculature. And in that case, all you really want is tissue for diagnosis. And that can be obtained either through open biopsy, laparoscopic biopsy, or even core needle biopsies done by an interventional radiologist. So it's whatever your institution is most comfortable with. Okay. So you do your biopsy. What do you look for on the biopsy and how do you manage those results? So it's important what you're looking for in the biopsy results are to get the biologic risk determinants out of the tissue. The most important of those is the NMIC status. You also want to look for 1P and 11Q deletions, but the most important thing you want to know is NMIC status along with the Shimada histology. Okay. So NMIC status, 1P and 11Q. Shimada histology. Okay. And what do we do now with those results? So that will tell you what risk category the patient falls into. And they can be either very low risk, low risk, intermediate risk, or high risk. It's divided about 50-50 between the low risk categories and the high risk category, and then a smaller percentage are intermediate risk. So essentially, NMIC status automatically puts you into the high risk group. Essentially. Not 100%, but that's NMIC and age greater than 18 months are the most important prognostic determinants for neuroblastoma. In patients with high risk tumor, they receive aggressive chemotherapy, including peripheral stem cell transplant times 2, as well as aggressive surgery with the goal of a greater than 90% resection of the tumor, followed by radiation, immunotherapy after the chemotherapy, and potentially retinoic acid therapy. So very aggressive therapy for the high risk group. All right. And what's the treatment for intermediate risk? So intermediate risk tumors get varying cycles of chemotherapy based on the biologic risk factors that they have. In terms of surgery, the goal at the time of debulking or resecting the primary tumor is to achieve at least a 50% response. And that is from the initial volume of the primary tumor. So the combination of neoadjuvant chemotherapy and surgical resection should achieve a greater than 50% reduction in the primary tumor size. Okay. What about the low risk group? The low risk group, depending on the actual age of the patient and how it's diagnosed, could potentially be followed simply with observation. Jed Nocturne led a study through the Children's Oncology Group looking at patients less than six months of age with either a prenatally diagnosed or shortly postnatally diagnosed localized mass. Those patients can be observed with the expectation that the vast majority of them will avoid any type of surgical procedure. And the child that has metastatic disease, how do you manage those patients? So typically those patients would receive four or five cycles of neoadjuvant chemotherapy and then be reassessed. If the tumor is responding, and specifically if the metastatic disease is responding, then one would attack the primary tumor site with a resection. And many, including myself, would advocate for attempting a greater than 90% resection. If the metastatic disease is progressing, then the surgery is not indicated. MS disease is specifically for patients who have a primary site with metastatic disease to the liver, the skin, or the bone marrow, specifically not bone, not cortical bone, and is less than 18 months of age. In those patients, simple observation can be the treatment path. If they progress or they end up with respiratory issues because of an enlarging liver mass or something like that, then you might elect to treat them because of the complication of the size of the tumor. But the tumor itself usually does not have to be treated. Can you biopsy the skin lesions? You can biopsy the skin lesions and that will give you the diagnosis. Okay. So that's neuroblastoma in 10 minutes. Here are your clinical pearls. Neuroblastoma is the most common extracranial solid tumor in children. It often presents with an abdominal mass. Workup involves abdominal ultrasound, blood work, MIBG scan, and cross-sectional imaging. Get tissue through open, laparoscopic, or core needle biopsy. Post-biopsy staging is stratified into very low, low, intermediate, and high risk. N-MIC amplification and age greater than 18 months are poor prognostic factors. And finally, treatment is based on risk. Low risk, operate or observe, age-dependent. Intermediate risk, chemotherapy, and a more limited surgical resection. High risk, neoadjuvant chemo, surgery, radiation, peripheral stem cell transplant, and immunotherapy. Now that you've listened to the essentials of neuroblastoma, be sure to listen to the full audio chapter where Dr. Von Allman is joined by Dr. Erica Newman and Dr. Anthony Sandler to discuss neuroblastoma management in greater detail. Let us know what topics you'd like covered and any other thoughts you have on the Stay Current app. Or give us a shout out on Facebook and Twitter. This chapter is created and edited by Todd Ponsky, Alex Kassar, Alex Skibbins, and myself, Ray Hanke. Remember, knowledge should be free.

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