Neuroblastoma

Welcome to the latest episode of Stay Current in Pediatric Surgery, a multimedia production designed to spread the latest knowledge freely. This chapter is created and edited by Todd Ponsky, Alex Kessar, Alex Gibbons, and myself, Ray Hanky. Does your head spin when you think about neuroblastoma, low, intermediate, high risk and how the management changes for each? Join us as we break down this complex subject with pediatric oncology experts from around the country. Welcome to Stay Current in Pediatric Surgery. This is Todd Ponsky recording live from Cincinnati Children's Hospital. And today we're going to be talking about a topic that I don't know much about and we get to hear the real experts tell me about what's new in neuroblastoma. Neuroblastoma is a common problem that we all deal with and it seems like the the way to manage this is changing day by day. So we finally got some experts to put some clarity on this. First, I'd like to introduce Dr. Dan von Allman, who is the surgeon in chief here at Cincinnati Children's Hospital and is our expert when it comes to neuroblastoma. We also have Dr. Erika Neumann, who is at CS Mott Children's Hospital in Michigan and she has a clinical focus on oncology. And finally, we have Dr. Tony Sandler, who is the surgeon in chief at Children's National Medical Center and he also has a focus in oncology and neuroblastoma. Let's dive right in. We're going to, just like we always do, we'll pick some cases that are pretty common and sort of hit on some of the the nuances of the disease. Dan, you're in clinic and you are seeing a prenatal consultation with a woman that has a 26-week fetus that has a prenatal diagnosis of a left-sided super renal mass. Otherwise, the ultrasound is normal. What do you do with that? What is your differential diagnosis with a left-sided super renal mass? Uh, the most common things we think about, first would be an adrenal hemorrhage. That's more common if there's some history of stress to the fetus or something like that, but certainly that's one of the more common things that we think about. And then obviously, if it's solid or cystic mass, you also have to consider the possibility of a neuroblastoma. The other differential diagnosis include things like uh pulmonary sequestration, which can occur below the diaphragm as well as potentially a renal anomaly that's been misdiagnosed as a super renal mass. So, Erica, what do you tell the family now? So they come to you, you've got this super renal mass, you don't know what it is. How do you counsel them? So, I mostly I'm quite reassuring at this stage. It's still a bit early. I think you said the patient was at 26-week gestation? Yes. Yeah, so it's a little early. We still have some time to go before delivery. And I don't really do anything before the delivery. I don't get any more studies and when the baby is born, then I'll ask the family that if it's not born at our hospital, I'll ask the family to please get in touch with me. If it's here, I'll say, let me know when the baby is born and I'll come up and meet the family and the and the baby after the baby is born. I think it's important to reassure and help the mom understand that the priority during the pregnancy is the mom. And once the baby is born, then we'll learn more and the first thing we'll do is get more information once the baby is born. Tony, would you add anything else to that in your consultation? Yeah, I agree very wholeheartedly with Erica and reassurance. I think often when we're doing these prenatal diagnoses, we get too carried away with the details of the disease and uh we get parents all frightened about it. The other thing that I think is important to remember is to ask the family whether there's any familial history of neuroblastoma. I know it's very rare and it only occurs in about 1% of patients, but a familial history of neuroblastoma would help probably guide the diagnosis of a super renal mass in this mother. That's a great point. Okay, so you did that, Tony. Now what? Well, the the obviously the the pregnancy should go along as expected. The mother should uh have a normal prenatal care. And then once the child is born, we start uh doing some postnatal studies. And of course the first one that you would do is examine the child making sure that this is a otherwise healthy child that's asymptomatic. And if that is the case, then I'd probably start off with an ultrasound of the child's abdomen. The child then is born at 38 weeks. You would get the ultrasound. Um, would you get any CT scan other MRI or any other axial imaging, Tony? Uh, I wouldn't unless um the urine caticolamines are are high and unless you're concerned about something unusual. If it's depending on the size of the lesion, if it's probably let's, let's for argument's sake, call it a 3 cm lesion. I would probably just follow with ultrasounds and urine caticolamines. If the caticolamines are high, then one, we can start discussing whether perhaps an MIBG would be worthwhile, and that would be my next step if I was going to work this up further. I would agree completely with Tony. I think that the, you know, the ultrasonographers and the radiologists are actually quite good at at identifying uh what looks to them like a adrenal hemorrhage. And you can, while you can't be sure, uh it certainly helps to get the urine caticolamines to uh direct the counseling of the parents one way or the other. If the urine caticolamines are high, then you're going to want to counsel the parents about potentially more likely neuroblastoma. But if they're normal and the ultrasonographer is convinced that this is an adrenal hemorrhage, you can really be very reassuring, which doesn't mean you shouldn't follow it, but you can be um, you can be more definitive with the family about the risk of a tumor. All right, so I'm going to repeat what I hear so far up to this point. Reassurance during the fetal period. All you need to get is the ultrasound. After they're born, you get a follow-up ultrasound postnatally and urine caticolamines. Maybe if those are elevated, you would get an MIBG, but no need for a cat scan at this point. Any need for a bone marrow biopsy? You know, the only time I would do a bone marrow biopsy is if the MIBG is positive showing bone metastasis. Then I think it's worthwhile doing a biopsy because at that point you may want to determine whether this is a Nmic amplified neuroblastoma, which in all reality in these prenatal diagnosis is extremely, extremely rare. At this point, you have an ultrasound and urine caticolamines that are elevated. Tell me about the MIBG scan. What are you looking for on the MIBG scan, Erica? I'm mostly looking to characterize the primary lesion and then also to understand if there're any other areas of disease. What are the more common areas for metastasis? So, in a neonate or in the perinatal phase, the most common areas would be liver, bone, skin, and lymph nodes. All right, so, Dan, you have an MIBG that lights up only at the super renal mass. Yep. Uh, do you observe or do you operate? So, uh that is a a discussion you have to have with the family uh because the uh data from the Nocktern study would suggest that you can confidently observe these patients uh, but you have to observe them carefully with ultrasound studies looking for growth, but that many of these patients will actually be spared any surgery if you just watch uh even if you have a by laboratory studies that confirm neuroblastoma with an MIBG and positive urine caticolamines. On the other hand, families are sometimes unwilling or uncomfortable uh having a mass in their newborn and they want it out. But I would suggest that probably most if counseled with the current data would be willing to simply observe this. Yeah, I agree with that completely. I think that Dr. Nocktern's studies have been very reassuring that um particularly in neonates with proper surveillance that most of the children don't require surgery or chemotherapy. For the first year of life there's a lot of imaging and monitoring that goes on, but um most of these children can be spared surgery. I think one of the other things when you speak to the family, it's really important to reassure them that even if the mass increases in size and you take it out, it is likely to be a very, very low risk tumor. So it's very uncommon to have a bad neuroblastoma. It's possible for sure. Yeah, appears in a newborn. A new born. As you're watching because cereal ultrasound studies and it begins to increase in size and you'll like to take it out, it's still likely to be a low risk too. Okay. All right. Todd, if I can also take a shot at that, the the number that I quote the families from that original study is that they um, of the, I think it was 84 patients that they observed, 16 underwent resection for either growth or some uh other reason, in other words the families didn't want to wait. And so that's about a 20% resection rate of those of ones that underwent observation. And of those patients, um, I think it was like about 98% had event free survival and 100% had overall survival. So you're quoting a study that was done uh with very good outcomes and I think it's very reassuring for the families to hear that there's data. Great. Agree. Yeah. So how often do we check ultrasound and urine caticolamines and for how long? So it's pretty intense for the first year. Um, they're getting them at birth, then at three weeks, six weeks, 12 weeks and then as long as things are stable, then they get spaced out from there all the way to one year. Then we stop at a year. Then a year it becomes something more like every six months. After every six months, then a year, I think it's more than up to the oncologist how they would ordinarily do that. But I do think that if they're followed by the oncologist, they tend to be followed long-term, not long-term, but they they're followed for probably more than a year. Um, many of the lesions resolve. So they're gone and once they're gone, then you get some ultrasounds after that to make sure they're gone. The only caution I would raise is that we had a case of a child who presented with exactly this scenario, was observed, the adrenal mass went away and age at age three she presented with widely metastatic high risk neuroblastoma. Wow. So that's a cautionary tale, but I I still think that the overall outcomes are really, really good and you should just observe these. Dan, that is a very interesting case. Um, you know, I that does actually bring caution to our general approach to managing these. The other thing that I'm always um a little bit cautious about, I'll say is when I'm counseling the patients and as we're getting through this first year, it's always a little bit um unclear to the families because we don't have a biopsy and really what we're going by is how the lesion looks on the ultrasound and on the CT scan and the caticolamines, but you don't know really what the tissue diagnosis is until we in when and if we take the mass out. And so I'm always cautious in saying, like all the data we have, it looks like a neuroblastoma. But I will say the last one of these that I had at the 12-month scan it got bigger. And we took it out and it was a ended up being a sequestration. And so I was glad that we had kind of prepped the family that this is most likely neuroblastoma but it could be something else um because after going a year thinking your baby has a neuroblastoma and then you end up with pulmonary sequestration that was below the diaphragm, you know, we just I I think it's just important to make sure that we are very reassuring to the family that based on all the information we have, this is what this probably is, but that we have to have some level of uncertainty because we we don't biopsy these kids. So, the only thing that I would discuss is when does one operate and I'm not exactly sure what the size is. I've always used the 5 centimeter size as an indicator for surgery, but I'm not sure um, that is sort of my cutoff. If it's obviously getting smaller, I wouldn't operate. If it's getting bigger, I do operate, but I'm not sure what my other colleagues on this esteemed panel, what size they use. I I would agree with you uh Tony. I think that if the mass, first of all, if it's increasing in size, then that in and of itself is concerning and there are specific criteria, but once a mass gets to be 5 centimeters, then I I personally would be recommending to the family that we take it out. I agree with that and then as we're surveying, I use the original criteria of, you know, if it goes increases in more than 50% volume. And then the other thing we look at are the urine caticolamines. And uh 50% increase in either the VMA or HVA would prompt us to start thinking more about surgery. That's a great point, Erica. That's I think it's important that you're not just doing ultrasounds, you're continuing to monitor urine caticolamines. So, uh Dan and I just came up with the same exact question at the same exact time. So Erica, if you do decide to remove it, would you do it laparoscopic or open? Yeah, I think laparoscopic, if particularly if it's less than 6 centimeters, I think it's worth a shot to put a scope in and take a look. Um, I was glad we were able to do that for this baby. I think that sequestration ended up being about 3 and a half centimeters. And it came out very nicely with a laparoscope. The child went home the next day. Do you need to do any lymph node sampling? I don't think lymph nodes give us any more information than we already have in neuroblastoma from the cross sectional imaging. I agree completely. Uh unlike Wilms tumor, the lymph node status of neuroblastoma, um is not as important in the change of therapy. The biology of the neuroblastoma, which I'm sure we'll discuss later is more important than lymph node status. Erica, let's say the child has skin lesions and liver mets. Now what? Now things get a little different. This would what we're calling now staging the old stage 4S and I would say I'm still reassuring at this point with the family. The biology of these tumors tend to still be good. These aren't bad neuroblastomas. There is a scenario where things could get bad and that's if the liver is filled um and engorged with tumor. What what exactly can go wrong when the child has a liver full of tumor? The most common thing that we worry about is is the mass, is the mass effect of the tumor in the liver, which can be really dramatic and causes respiratory compromise. And that's the problem that the a newborn would face is increasing uh ventilatory requirements and uh inability to ventilate once the tumor gets large enough. So how do we treat these these children? If they're not in any distress, they're treated with my favorite protocol, which is aggressive observation. That is you don't necessarily have to uh you don't necessarily have to do anything other than watch them, but once they begin to get in trouble, then you certainly want to have tissue and make sure that it is in fact MS and not a high risk tumor and you can treat them with either chemotherapy or radiation if you get to it early enough. If the child acutely decompensates, then doing a decompressive laparotomy is also described as a potential emergent therapy for kids who have respiratory compromise. See, you mentioned if we have tissue. So it is not a requirement to biopsy even the skin lesions in these children? I think that in most cases and I'd be interested to hear what what Erica and Tony say, we want, we would get tissue to confirm the diagnosis and get some biologic information. Yeah, I think uh if you have the classic findings with uh high urine uh epinephrin, norepinephrin or caticolamines. And you have the blue blebs on the skin uh with a liver with liver metastasis and a uh adrenal mass, I don't think you really even have to biopsy that kid. However, if you're taking the kid to do something radical like a laparotomy uh to place a silo to decompress the abdomen, then I would certainly biopsy the easiest lesion. I'm not sure I would biopsy the liver uh because once you get bleeding in a in a newborn liver, it's very hard to control. So I would take another lesion other than the liver unless the liver is the easiest to get to. But yeah, I completely agree with Dan, it's uh observation. I haven't in my career had to open an abdomen and place a liver in a bag or anything like that. I agree. Um, I know that our oncologist have often asked us to do a biopsy and they like to get that because if in the rare instance the Mican is amplified, it changes them then from MS to M. And so for that we're sometimes faced with should we be going into the abdomen? If we can avoid particularly in neonates going into the abdomen for a biopsy, I think we can decrease the risk of that abdominal compartment syndrome postoperatively. So, Erica, Tony, let's talk about another case or another child that we that we often times see and this is a three-year-old who presents with a large central abdominal mass. You know, the classic history, grandma noticed in the tub giving the child a bath and they come in uh with this large abdominal mass, otherwise healthy child. How would you work that kid up? Erica, what's your approach? First, obviously, we do a good history and physical exam, finding out if the child has had any other illnesses, any family history, past medical history. Uh, I saw a child today that had diarrhea. I thought that was interesting because we, remember I've always read that you can get, you know, VIP secretion and severe diarrhea from neuroblastoma, but I had not seen that and I always ask about that. And then with respect to trying to to understand more about the mass, I'll typically start with an ultrasound. Um, I get an ultrasound to to see if I can get a clue on whether this is a solid or a cystic mass. If it's solid, then most likely we would then move on to cross sectional imaging. Um, and I usually get a CT scan with PO and IV contrast just because I'm more comfortable reading a CT scan. While we're waiting on the CT scan and and the contrast, we'll get some blood work. Uh routine blood work is, you know, CBC, a comprehensive panel. Um, I'll usually get um tack on uh amylase lipase LDH and just a standard blood work that we would be getting for anyone that would have some um abdominal masses. And so, um, we then send the urine caticolamines and I'd wait and see what what all that showed. Great. Um, Tony, anything you would add to that initial evaluation? No, I agree completely. Um, you know, when you're initially seeing a child with an abdominal mass and you're not sure what it is, I think it's very reasonable to go ahead and get an ultrasound. Uh if it turns out to be Wilms tumor, the ultrasound is already done because you want to see if there's any venous extension of the tumor. And as Erica clearly stated that it you also want to be able to tell whether this is a cystic or solid mass. Yeah, that venous extension thing for the Wilms is a great point. I that's uh that's a great reason to get the ultrasound. But so you get a CT scan and it shows a big 10 cm mass that encases the aorta and the celiac axis. Micro calcifications, more solid than cystic. Now what would you do? Uh Tony, what's your group's workup? So Dan, what you're describing uh is an L2 international neuroblastoma risk group uh classification of the local tumor. So this is obviously going to need necessitate a complete workup and obviously the oncologist now get involved and are really key to the the further workup, which includes uh uh probably a bone marrow, um the the CT scan already being done. You're getting a technetium scan or MIBG scan. Um, I also like a CT scan because I can read it better. An MRI is certainly an option. You also want a chest CT because you want to rule out metastasis. Uh and then also a head CT can be indicated if there's any clinical symptoms that the patient may have. So now you're talking about the staging of the disease and then of course the final aspect to staging the disease is getting a biopsy uh for pathology and and of course the biology in the case of neuroblastoma. So how about pet scans? Do you do either of you guys get pet scans? Our guys are very fond of pet scans. We're also very fond of pet scans, but the question is for the initial workup, a pet scan is not going to be my workup. An MIBG scan will be. And I'm not sure a pet scan will have any benefit over an MIBG scan in neuroblastoma. Correct me if I'm wrong. No, I think, I think you're right. I agree with you. I think the rationale that's often given is that 10% of neuroblastomas are not MIBG avid. So potentially they would be pet avid even though they're not MIBG avid and you might also pick up uh metastasis that way. So I agree with you. It's sort of uh we get them and we get lots of them, but um, but it may or may not be necessary, especially if it's MIBG avid then you have a study that you need to not only make the diagnosis and identify mets but also to follow it, I think. Dan, I think you outlined that clearly. If it's certainly if it's 10% and your MIBG is negative, then I would agree with pets, I wouldn't argue against a pet scan. Erica, how about you? Do you guys get them? No, we don't get them. They're very few scenarios we get them where um every now and then we've we have a child where the primary lesion has been resected and there's a funny looking um soft tissue area that is MIBG negative and we're trying to decide if this is a local recurrence or um nothing or scar. And so they'll get a pet scan in a scenario like that, but that wouldn't be part of our routine initial diagnosis workup. Uh Tony, you mentioned getting tissue, obviously it's the sort of the key or final step in doing the staging. What do you think about the options for for getting tissue? Do you and and Erica, do you do y'all do percutaneous biopsies? Do you do laparoscopic biopsies? Do you do open biopsies? Lots of different ways to get tissue. So, uh Erica, I'm sure you'll probably contradict me, but this is sort of my approach. Um, I'm sort of old fashioned in this way because I've been, you know, trained to get that size of tumor that can be biopsied uh safely and that can uh give the necessary tissue uh for further studies and bio biology of the tumor. And so I've always done a retroperitoneal approach to a large mass and done an open biopsy. I am uh a little reticent to do a transperitoneal approach and biopsy a big tumor uh laparoscopically because I'm not sure I can control the bleeding as well as a retroperitoneal approach. You could do a percutaneous biopsy. You would have to do multiple uh uh percutaneous biopsies. Um, and I'm not sure um the tissue collected is adequate for biology. So, uh people also say you can take bone marrow and you can get the Nmic amplification on bone marrow, but there's more to do than just Nmic. There's the alktion to look for. There um is of course adequate biology for pathology. And of course you um, you know, you really do want uh to look at the deployed status of the tumor as well. So, right now I am still doing open biopsies unless there's some reason that the child is very sick and they can get Nmic amplification of the bone marrow. That's been my strategy right now. I'm sorry for the long-winded answer. No, that's awesome. That's great. Can you explain to me what you mean when you say you do a retroperitoneal biopsy?