# Topics in 10: Neuroblastoma — GCMD Library

Drs Daniel von Allmen, Todd Ponsky and Rae Hanke come together to provide you the essentials on the diagnosis and management of Neuroblastoma.

Intro and outro tracks are adapted from "I dunno" by grapes, featuring J Lang, Morusque. Artist URL: ccmixter.org/files/grapes/16626

Neuroblastoma:

Clinical pearls:

Type: podcast · 10 min · posted 2020-12-30 Canonical: https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659 ## Chapters - [0:00](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=0) Introduction and Clinical Presentation - [1:32](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=92) Diagnostic Workup and Staging - [3:53](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=233) Surgical Approach and Biopsy - [5:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=345) Risk Stratification and Treatment - [9:00](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=540) Clinical Pearls Summary ## Statements - "Neuroblastoma is the most common extracranial solid tumor in children" — Rae Hanke (epidemiological) [0:00](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=0) - "The majority of neuroblastoma cases occur in children less than a year old" — Rae Hanke (epidemiological) [0:00](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=0) - "Younger patients are often picked up prenatally on ultrasound or as a solid abdominal mass in two- or three-year-olds" — Daniel von Allmen (clinical) [0:41](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=41) - "Patients with metastatic disease may present with bony pain or neurologic symptoms from cord compression" — Daniel von Allmen (clinical) [0:41](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=41) - "Catecholamines (urine or serum) are one of the most diagnostic laboratory tests for neuroblastoma" — Daniel von Allmen (clinical) [1:07](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=67) - "Cross-sectional imaging (CT or MRI) is obtained after initial ultrasound and laboratory workup" — Daniel von Allmen (clinical) [1:39](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=99) - "MIBG study is helpful for confirming neuroblastoma diagnosis and demonstrating metastatic disease" — Daniel von Allmen (clinical) [1:39](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=99) - "About 10% of neuroblastomas are MIBG negative" — Daniel von Allmen (clinical) [2:20](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=140) - "Some centers obtain a PET scan for MIBG-negative cases to look for tumor uptake and metastatic disease" — Daniel von Allmen (clinical) [2:20](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=140) - "The INRGSS staging system allows stage assignment before any invasive procedure" — Daniel von Allmen (guideline) [2:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=165) - "Localized tumors without image-defined risk factors are categorized as L1" — Daniel von Allmen (guideline) [2:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=165) - "Localized tumors with image-defined risk factors (encasing nerves or vessels) are L2" — Daniel von Allmen (guideline) [2:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=165) - "Tumors with metastatic disease are categorized as M" — Daniel von Allmen (guideline) [2:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=165) - "MS category is for children less than 18 months with metastases to bone marrow or skin" — Daniel von Allmen (guideline) [2:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=165) - "The INRGSS was created to allow studies from different centers and countries to be compared based on pre-surgical staging" — Daniel von Allmen (guideline) [3:36](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=216) - "The prior staging system required tissue diagnosis before assigning a stage" — Daniel von Allmen (guideline) [3:36](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=216) - "A patient with a resectable adrenal mass and positive MIBG without metastases can be treated with primary resection via laparotomy or laparoscopy" — Daniel von Allmen (clinical) [4:06](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=246) - "For 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 Allmen (clinical) [4:44](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=284) - "NMIC status is the most important biologic risk determinant from biopsy tissue" — Daniel von Allmen (clinical) [5:14](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=314) - "1P and 11Q deletions should be assessed in biopsy tissue along with Shimada histology" — Daniel von Allmen (clinical) [5:14](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=314) - "Neuroblastoma risk categories are very low risk, low risk, intermediate risk, or high risk" — Daniel von Allmen (guideline) [5:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=345) - "Risk distribution is approximately 50-50 between low risk categories and high risk, with a smaller percentage intermediate risk" — Daniel von Allmen (epidemiological) [5:45](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=345) - "NMIC amplification and age greater than 18 months are the most important prognostic determinants for neuroblastoma" — Daniel von Allmen (clinical) [6:06](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=366) - "High-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 Allmen (guideline) [6:06](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=366) - "Intermediate risk tumors receive varying cycles of chemotherapy based on biologic risk factors" — Daniel von Allmen (guideline) [6:51](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=411) - "For intermediate risk tumors, the surgical goal is at least 50% response from initial primary tumor volume combining neoadjuvant chemotherapy and surgical resection" — Daniel von Allmen (guideline) [6:51](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=411) - "Low risk patients, depending on age and diagnosis timing, could be followed with observation alone" — Daniel von Allmen (guideline) [7:22](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=442) - "A 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 Allmen (guideline) [7:22](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=442) - "Patients with metastatic disease typically receive four or five cycles of neoadjuvant chemotherapy and are then reassessed" — Daniel von Allmen (guideline) [7:55](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=475) - "If metastatic disease is responding to chemotherapy, the primary tumor site should be resected with attempted >90% resection" — Daniel von Allmen (guideline) [7:55](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=475) - "If metastatic disease is progressing on chemotherapy, surgery is not indicated" — Daniel von Allmen (guideline) [7:55](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=475) - "MS 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 Allmen (guideline) [7:55](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=475) - "MS 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 Allmen (guideline) [7:55](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=475) - "Skin lesions in MS disease can be biopsied to provide diagnosis" — Daniel von Allmen (clinical) [8:55](https://library.globalcastmd.com/watch/topics-in-10-neuroblastoma-1659?t=535) ## Transcript 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. --- Not medical advice · citation policy: https://library.globalcastmd.com/ai