While 80 to 90% of peripheral lymphadenopathy in children is benign and self-limited, no clinician wants to miss signs of a malignant process. Here's help from pediatric hematologist-oncologist Rohini Jain, MD, who offers tips and tools for picking up on lymphoma, including a strategy for asking essential history questions and a physical exam method that leads to useful details on problematic lymph nodes. Jain describes first workup steps, such as lab tests and imaging studies, and provides a list of worrisome signs that warrant swift referral. Bonus: Learn about new treatment approaches that have reduced long-term toxicity for survivors of childhood lymphomas.
OK. All right. If, uh, and if anyone has any trouble hearing, um, please feel free to let us know. Um, and then there will be a Q&A session at the end, um, where I'm hoping we can have a discussion and just answer any questions, um, that you all might have. But, uh, briefly, just to tell you a little bit about myself. Um, my name is Johini. I'm currently one of the pediatric oncologists here at UCSF. Um, I actually see Patients, um, in all three of our kind of clinic sites which include Walnut Creek, Oakland, and San Francisco, but I am primarily East Bay-based. Um, a little bit about my background, I grew up here in the Bay Area in Fremont, so not too far away, um. Uh, from UCSF Benioff, um, I did my medical school at UC Davis. I did my pediatric residency out in Boston at the Boston Combined Residency program, so I got to work both at Boston Medical Center as well as Boston Children's Hospital. Then I, uh, completed my PT Monk fellowship, um, here at UCSF on the San Francisco side, uh, which I just completed, uh, last year, and then Now, as I mentioned, one of the oncologists, um, part of the practice, clinically, I'm interested in lymphoma, um, though I do see a little bit of everything, um, from a research perspective, I've been quite interested in thinking about medical education, um, and how we teach about structural inequities that affect our patient population, as well as looking at disparities to access within lymphoma care. So, That is a little bit about me, and I will go ahead and get started with the presentation. So, uh, today I was hoping to talk a little bit about, um, our approach to lymphadenopathy, really describing kind of the characteristics that we think about when we start worrying about when is lymphadenopathy not benign and when, um, does it require for the workup, um, and when are we sort of starting to get concerned about lymphoma, um. Um, as a disease process. And then I was going to end with a little bit of an overview of how we think about lymphoma in our pediatric and young adult population, as well as the recent, um, some recent, um, uh, progress that we've made in terms of our treatment approach and risk stratification for them. Um, so I will go ahead and get started. So when we think about, uh, lymphadenopathy, um, it's quite a broad term and um it really, um, Uh, really describes, um, you know, a set of regions, um, within our body where this lymphadenopathy can occur. I'd like to pull up these figures, um, just so that we can appreciate how many different lymph node, uh, basins or sites that exist in our body. Um, I think primarily when we think in the pediatric and young adult, uh, population, we think a About the head and neck or cervical region for lymphadenopathy, as there are a lot of tracts within this area specifically, um, that can lead to lymphadenopathy, secondary to a number of reasons including medications, infections, and then of course malignancy. Um, and so in the head and neck area in particular, there are many regions that we think about. Uh, for lymphadenopathy. Uh, and I kind of outlined the head and neck area more specifically here on the right, just thinking about the many different, uh, locations where I tend to do a deeper exam to really try to understand where the lymphadenopathy is. Um, and when I go into the physical exam, I'll kind of discuss a little bit my approach to how head to toe I sort of assess. these regions, but just again wanted to kind of give a pictorial representation of all the different areas where lymph nodes can exist. So as I mentioned here on the right, we have the head and neck area, which is kind of outlined in particular details starting up with the posterior ricular and going all the way down to the supracovicular regions. But in addition to the head and neck, there are many other regions where lymphadenopathy can exist with the biggest ones being Um, axillary, as well as inguinal and popliteal. So these are the areas kind of throughout the body where we're sort of assessing the lymphadenopathy and making the determination, or do we think this is kind of a benign process or more concerning for a malignant process. When we kind of think about lymphadenopy, there are a couple of general principles that I've kind of always try to keep in the back of my mind as I'm sort of thinking about or approaching a patient or family that um it's concerned about an elevated lymph node. For the most part, peripheral lymphadenopathy in children is usually benign and self-limited. This actually accounts for 80 to 90% of cases, um, as much as I think cancer, um, is not rare because I see it every day, it really is a rare process and most of the lymph lymphadenopathy that we see in otherwise healthy children is benign. How we kind of determine this urgency or extent of evaluation is really defined by a couple of features, including how ill does this patient appear, and whether or not there are clinical features, either on exam or in lab that are more suggestive of a malignant process. But in general, we take a very stepwise approach um to how we assess lymphadenopathy, um, which is guided a lot by a detailed history and a careful physical examination, which we'll go through in the next couple of slides. Mhm There we go. Um, so thinking about, um, the history, I like to think about sort of three main buckets of questions or sort of detailed, uh, information that I'm trying to assess, um, when I think about lymphadenopathy. First one being as we do sort of with any patient or family that comes in with a specific complaint is really getting a good detailed HPI or history of present illness. Similar to a lot of the questions that we're probably already asking about lymphadenopathy. I'd like to key in on location, you know, is it localized just in 11 spot? Is it generalized? Do we feel like there is lymphadenopathy sort of all throughout the body? Thinking about timing and onset, is this something that Has come up relatively within the past month, um, and has not changed. Is it something that has been pleasant for many months or years and hasn't changed? Or is it something that, you know, is relatively new and seems to be changing. So trying to get at really specific details of what is really the time course of this lymphadenopathy and has anything changed recently, um, particularly thinking about changing size and changing in sort of how it feels on exam, which we'll get into. Um, the other thing I like to, um, get a really good detailed history about is any signs of, uh, any history or signs of infection. As we know, lymph nodes are really the draining sites, um, in our body for when Um, our body senses or see something foreign and as a reaction, um, you know, you can get benign reactive lymphadenopathy just due to, uh, infections sort of in those areas. So for example, if someone is coming in with the concern of an abnormal or what they perceive as a um enlarge lymph node in their neck, asking a really good head and neck infectious history can sometimes help tease out details of are we worried or are we not worried. For example, if someone's had a recent sinus infection or colds, um, or, you know, any sort of obvious trauma to that area, that obviously will change the way we sort of think about that lymphopathy. The other thing I always ask about is constitutional symptoms. So these are symptoms or systemic symptoms that we describe as fever, weight loss, or night sweats, and you know, within our um kind of oncology field, there are actually specific um criteria to this that really raises our concern for um abnormal lymphadenopathy. So when we think about Weight loss, we think about unintentional weight loss, and weight loss that is at least 10% change from their baseline. So, for example, if someone was 100 pounds, and all of a sudden, in the past two months, they are 90 pounds or less, that sort of meets meets that criteria of 10% unintentional weight loss or less. The other thing I ask about is night sweats. Um, Night sweats can mean um different things to different people. So I do like to sort of describe this phenomenon when we think about night sweats associated with lymphoma, we can really think about like drenching night sweats. So asking patients and their families. Like when they wake up, do they feel like they've soaked through their sheets, soaked through their pillowcases, you know, the occasional little bit of sweat at night it's not really what we're talking about. One thing about night sweats, you truly mean sort of just like drenching through their clothes, um, sweating. Um, the other thing I like to ask about that's very common in our pediatric population is dental issues, particularly with cervical lymphadenopathy. Um, there's been a number of times where we, you know, get a more detailed dental history and realize there's actually an underlying tooth abscess or cavities or abnormal dentition that could actually be leading to lymphadenop in that area. And then when you do your exam, Um, you know, especially over the area where that lymphadenopathy is thinking about any obvious signs of trauma, rashes, or skin lesions that could be explaining, um, increased lymphadenopathy in that area. Uh, moving on past the HPI, just thinking about other causes of lymphadenopathy, you know, besides, um, Uh, malignancy or besides infectious disease, thinking about just exposures, um, that could lead to lymphadenopathy. So I think we've talked quite a bit about sick contacts and other sort of uh viral bacterial causes, um, that could cause lymphadenopathy. But the other thing, um, just kind of putting on my ID hat for a little bit, um, I think about is just exposure to, you know, unpasteurized milk or undercooked meats, different animals, um, you know, I think one common thing that we C is, um, you know, lymphadenop a secondary, um, to cat scratches or cat bites. So think about like Bartonella, other types of exposures to farm animals or um anything else that could um expose their infectious risk, thinking about travel. History, um, one of the kind of more common causes of lymphadenopathy, um, you know, can be tuberculosis. So thinking about, you know, recent travel history, thinking about immigration status, thinking about other things like that can also help, um. Uh, also help us sort of tide, um, determine an ideology for the lymphadenopathy, and then especially with our young adult, um, and, um, you know, older adolescent population asking about sexual activity and sexual history, seeing if there are any risks for STIs, um, as a sort of cause, especially for inguinal lymphadenopathy. Um, and then taking, you know, a step back and looking globally at this patient and family, really diving into the past medical history, thinking about immunization status, you know, are there, are they at risk for any, um, Any particular diseases due to their immunization status and also asking if we get medication history. Um, common, you know, antibiotics that get prescribed like Bactrim or, um, Sera or trimethoprine, um, you know, can actually have lymphadenopathy as a side effect. So seeing and asking if there have been any uh recent um changes to medication and new medications, particularly in terms of travel, some of the anti-malarial medications can also cause lymphadenopathy, um, as a side effects, so just getting a good assessment of that as well. Perfect. Moving on to the physical exam, um, and thinking about how we, um, Um, how we sort of approach the physical exam, or we think about lymphadenopathy, as I talked about in, in terms of the history with the B symptoms or constitutional symptoms. Um, one thing I do like to take a look at, um, before I um before I examine or sometimes even before I walk into a room, and if we have that. Formation, um, is the growth chart and really looking at, um, you know, their weight, uh, their height, or any signs, um, that there might be any abnormal, um, growth before I go into the exam, particularly looking at weight loss to see if there, it does sort of meet that criteria of 10% of body weight. Next, I tend to do a pretty um comprehensive, um, uh, head to toe approach when I think about lymphadenopathy, keying in, um, you know, and doing kind of a more comprehensive exam or in the particular area where the lymphadenopathy is. But as I mentioned, in the beginning of this presentation and sort of in that diagram of where all the different lymph node basins are, um, I really do try to um assess to see if I feel lymphadenopathy outside of the area of concern for the family as well because oftentimes, um, Um, you know, there may be an obvious lymph node, um, that they feel in the head or neck region or, um, you know, under the armpits where they are sort of, you know, showering or feeling for themselves. But as we talked about, there are other areas like behind the knee or in the inguinal region that can have lymphadenopathy as well. So, starting from sort of head to toe, um, I do a pretty detailed, um, kind of Examination of the scalp, um, looking for different lesions or any signs of rashes in that area that could be explaining lymphadenopathy. There are certain malignancies outside of lymphoma like LCH or Langerhans cell histiocytosis that can sometimes first present with abnormal rashes or scalp lesions. Um, so I tend to take a, um, take my fingers and kind of comb through their hair to see if I feel anything abnormal. On their head or scalp. Again, looking for kind of signs or symptoms of infection or anything else in a particular area of concern that could explain lymphadenopathy. So taking a look for conjunctival erythema, signs of pink eye, signs of conjunctivitis, um, you know, using my scope to take a quick look in their nose to see if I see any signs of nasal obstruction or erythema and the turbinates doing a pretty good, um. Or a pharynx exam, again, taking a note of dentition, seeing any signs of pharyngitis, um, or anything else that could be present on the exam that could explain lymphadenopathy. And then, um, you know, some other sort of specific things that I listened for in terms, in terms of the chest region, uh, chest region, uh, excuse me, you know, different lung sounds like crackles, wheezing or stridor that could explain either asthma or type of, um, viral pneumonia. Um, if I do feel, um, you know, lymphadenop that I'm concerned about, the next thing I do is usually always feel the abdomen to see if I feel any evidence of an enlarged, um, liver or spleen, um, that could sort of go hand in hand with the malignant process or some type of consumptive process that's leading to lymphadenopathy, and again, doing a pretty good skin exam, uh, looking for localized lesions or rashes, um, in the area of concern. When I kind of do kind of my more specific uh lymph adenopathy um uh or lymph node examination, I kind of think about four different criteria to help me in my mind, um, kind of rate them how concerned I am about this particular lymphadenopathy. And so, First thing is location. Um, you know, do I feel just lymphadenopathy in one particular region or do I see sort of diffuse lymphadenopathy throughout the body? Um, you know, more generalized lymphadenopathy always sort of raises my concern, uh, for something more underlying or more underlying malignant. Process, um, as I talked about, if it's localized to either, you know, typically in the cervical region or the inguinal region, you know, always searching for pathology in that area of nodal drainage that could explain that, uh, lymphadenopathy outside of malignant process. One thing that I always, um, Um, think about a supra curvicular lymphadenopathy. That sort of particular site or region of lymphadenopathy is always concerning and should always be a referral, um, no matter what. There are no sort of local, um, Prostheses or local infections that should cause lymphadenopathy. The next thing I try to do is um get a sense of the consistency um for that lymph node on my exam. I'm really trying to determine, does it feel kind of, you know, rubbery? Is it mobile? Can I like move it between my hands, or does it feel kind of more hard or fibrotic or sort of attached to the underlying tissue? Um, and so the more fibrotic or firm lymph nodes tend to be the ones that My concern for malignancy, as well as those lymph nodes that feel like they're sort of stuck in place or attached to underlying tissues. Usually, reactive or benign lymph nodes are the ones that we can kind of move between our hands. Um, they feel mobile, they feel, um, sort of non-tender, not so, um, hard. This picture on the right is actually um a picture from a patient I had uh several years ago who ended up being diagnosed um with Burkitt's uh lymphoma, which is a type of non-Hodgkin's um lymphoma that is actually rapidly uh growing and, and progressive over a shorter period of time. Most lymphoma. are actually quite indolent and that they, you know, can be present and sort of slow grow, uh, for many months. Uh, but Burkis is one of the few lymphomas that can actually change quite rapidly. Um, and the size of the lymph node could be 1 centimeter one day and then could jump to 4 centimeters over a week. Um, but thinking about Um, just, you know, visually just looking at this, um, um, at the, at this lymph node without even feeling it. I think we can appreciate size, absolutely, you know, sort of hits that greater than 2 centimeter mark. Um, just taking a look at the shape, um, of this, you know, it's not your typical kind of round shape. It looks like it has quite irregular, um, Right some irregularity uh to the shape, um, and then when I did feel insulin filled on the exam, it was quite firm, um, and quite fixated and plates was sort of automatically hit sort of all of our check marks as for raising our concern for malignancy. And so Once we sort of, um, you know, have made the determination that, OK, this lymph node, you know, um, has enough features, um, you know, either on exam or with history that makes us concerned of something else being going on rather than, you know, a Reaction to an infection, um, you know, there are a, a couple of things that we, uh, recommend in terms of an initial laboratory workup as well as an initial imaging workup. Uh, so thinking about labs, um, you know, this is sort of the Kind of gamut of labs that we typically do on a first pass, and so that includes a CBC, um, a set of inflammatory markers which include ESR and CRP. Um, a set of electrolytes and tumor lysis labs, which I'll get into in a moment. Um, usually, the two most common infectious serologies that we send out for are CMV and EBV, um, as well as either a quant gold, um, or, um, TST to assess for tuberculosis and then thinking about that specific patient. It's its history or physical exam, um. Features we might send more dedicated testing. And so to go through a little bit about why we kind of choose these labs in particular for our first past CBC, um, you know, probably most obvious, um, thinking about if you're worried about a more malignant process and particularly a hematological malignant process like leukemia or lymphoma, um, you know, assessing for any signs of cytopenia, um, or, um, Uh, more than one cell line that's affected. So looking at the white blood cell count, looking at the platelets, looking at, uh, the hemoglobin to see if there's any abnormalities, um, in that, uh, in those lines, I will say that, um, lymphoma is, um, you know, different than leukemia in that, um, it does not always have to involve the bone marrow and so you may not see those cytopenias that you can. Typically think of as slam dunk for leukemia diagnosis, but it's still important to assess, um, to see if there are any, any abnormalities in the blood counts. And in addition, it is also a helpful marker to see if there are any uh signs on the CBC that raise our concern that maybe this is more of an infectious process. So looking for, um, you know, looking for, you know, that left shift. Um, in your neutrophils, looking to see if there's um an increase, um, you know, in, uh, lymphocytes that go along more with viral infections, looking to see if there are signs that are in or signs of, you know, allergic symptoms that could be contributing to lymphadenopathy, so assessing your Eosinophils. So that's sort of what we're looking for on the CBC to see if there's anything that can help explain the lymphadenopathy. Uh, the next thing that we look for is just signs of uh inflammation. So your ESR, or CRP, um, you know, these are acute phase reactants that are very non-specific, CRP, you know, being more useful and kind of the, um, sort of acute inflammation setting and ESR being a more um reliable predictor of chronic inflammation. There have been, um, Studies that show that, you know, very, very high and sort of persistently rising elevated. Uh, numbers of ESR and CRP can be associated with, uh, lymphoma, particularly Hodgkin's lymphoma, um, uh, is usually associated with a quite elevated ESR of greater than 50%. And so these are sometimes helpful to trend in that if we see that ESR CRP is elevated and continues to be persistently elevated over time or arises, um, you know, in the setting of lymphadenopathy, that could raise a concern of something else beyond just an infectious process going on. Uh, similarly, um, When we take a look at kind of our electrolytes, um, particularly the BMP, mag phosphoric acid and LDH, these are all markers of sort of tumor lysis or cell turnover. And so, um, when we are thinking about malignant processes like leukemia or lymphoma, where, um, cells are, you know, rapidly dividing, license licsing, and then turning over, whatever is inside those cells. gets released out into our blood. So if we think about the electrolytes that are typically housed within the cell, like potassium and uh phosphate, when there's concern for a malignant process, these numbers tend to be elevated. Um, and so that's kind of a quick and easy check for us to do, to see is our body showing any signs of this kind of increased cell turnover that might, that might raise our concern for malignant process. Similarly, with the infectious serologies, I think the two most common viruses that cause lymphadenopathy, particularly in the pediatric and young adolescent population, are EBV and CMV. Um, and so checking titers for those, checking, um, you know, a monospot to test for, you know, mononucleosis, um, can help sometimes determine, especially if the history goes along with that and that, you know, other kids at school also have, um, you know, signs and symptoms of Fatigue and fever, um, and malaise, um, you know, those kind of more infectious urologies for CMB and EVV can sometimes be helpful. Um, and then, as I mentioned, you know, based off of our specific patients, um, you know, history, you can do more dedicated workups. So, for example, with the history of a recent cat scratch or a re, um, or of an unprotectual unprotected sexual encounter doing further testing with, you know, STI testing or Bartonella can kind of, you can sort of direct your testing in that, uh, in that particular scenario. Um, and then, you know, in addition to labs, um, I think there are two sort of modalities of imaging that are very helpful, um, kind of off the bat, uh, to help with, um, sort of further elucidating. Are we kind of worried about this lymph lymphadenopathy or are we not? Um, you know, I feel like ultrasound has truly become the gold standard, um, for assessing lymphadenopathy due to sort of it's, you know, obviously no. Risk of radiation, um, to the child as well. It's relatively um easy to perform. And so I'll go through a little bit um on sort of what we look for in each modality and sort of what it can be helpful in determining. A chest X-ray, I primarily only order if I'm worried about any signs or concerns of a mediastinal mass or lymphadenopathy in the chest that I wouldn't be able to feel in my exam. I think it's sometimes helpful, um, Uh, for kids who have sort of generalized lymphadenopathy, um, which kind of automatically raises my concern for a malignant process, and I want to assess further if there's anything, um, in the mediastinal for supraclavicular lymphadenopathy or for any lymphadenopathy in the head and neck region that is greater than 2 centimeters. I would say the signs, um, on history that would make me more concerned for any type of minal mass or um hylar adenopathy is thinking about just sort of If I had a mass in my chest, what are some of the surrounding um structures, um, that could potentially be compressed by having something that shouldn't be there in the chest? And so, in particular, I think about, um, you know, the trachea, um, you know, lungs, your SVC vessels, and so looking for signs and symptoms of those on exam, a common way, um, That lymphoma can often present um in kids and young adolescence is a chronic cough, and that's due to a mitoinal mass that's sort of sitting right next to the trachea and compressing it. This is particularly can be seen in kids, uh, when kids feel like they have trouble sleeping or have more coughing at night because when they are, are supine, it causes more compression and leads them, um, to have difficulty breathing or respiratory. Dress only when they're lying down and sometimes they have those sort of classic symptoms of orthopnea when they're, uh, they need to sort of prop up their head when they're sleeping to sort of avoid these types of symptoms. So again, a chest X-ray, I really only order, um, you know, when I'm assessing for me like assessing for me total mass or have sort of that supporting history that makes me worry that is, are they having sort of signs or symptoms of compression in that area. Um, an ultrasound, um, you know, is quite versatile and useful for assessing kind of all locations of, uh, lymphadenopathy, and I think it would be really helpful in assessing the underlying architecture, the size, the shape, and the border of the lymph node. And so when I'm looking at an ultrasound report from our radiologist, these are really what I'm looking, uh, or kind of what I'm scanning the report for to see if I see any, uh, documentation of concerning signs. And so, When the radiologist sort of assesses the lymph node, I'm looking for them to describe one the shape, um, the border, um, whether or not they see, um, loss of the fatty hylum. The fatty hylum is the part of the lymph node where all of your, uh, vessels sort of emerge and, um, Uh, kind of vacate the lymph node. And so usually it's quite, uh, robust with, you know, arteries and vessels in that area. And when you sort of have a loss of that area, it's usually due to tumor invasion of the lymph node. And so I'm looking to see if they comment on the presence or loss of fatty hylum, um, as well as, um, the shape. And so up here on the left, we see an example of a lymph node. Um, two different lymph nodes. One, that is actually normal, and this is the one on the left here with my cursor. So normal lymph nodes are typically actually oval in shape. They usually have, um, quite distinct borders versus, um, an abnormal lymph node tends to be more round. You see sort of loss or irregularity of the border here. You don't kinda have that complete circle, but you see sort of a loss of the border there. Um. And then of course, they usually do give you a comment on the size or the appearance of the lymph nodes. And then this bottom right um is a chest X-ray that shows actually mediastinal widening, um, and this was in a patient of mine, uh, that actually presented with two months of a chronic cough. Um, and when we got the chest X-ray, we saw this mediastatal widening and then upon further imaging was found to have a mediastatal mass. Um, and so, you know, kind of putting this all together, um, you know, thinking about, you know, when is lymphadenopathy kind of worth, um, that, you know, more extensive workup, when is it, uh, you know, when should you refer, um, uh, you know, to, uh, to us, um, to get sort of a more Um, to get a second opinion on is this concerning or not, I think the bottom line in general is we are always happy to see any families or patients who are concerned about abnormal lymph nodes. It can sometimes get, um, You know, it can sometimes be tricky to, you know, to do the workup, have it reassure, uh, you know, have sort of nothing kind of come up with that, and family is just sort of needing a second voice to just sort of reaffirm everything that you've already said. And so, if there's ever any doubt or if there's any um Any ever um sort of increased anxiety or worry from families, we are more than happy um to see, um, and really provide that reassurance. I think it's actually one of my favorite things to do is to tell someone that they don't have cancer, and so we're more than happy to help in that regard. But, you know, as sort of a, a list of things that, um, you know, we truly do get worried about and absolutely, um, Think uh uh for the workup. And so to summarize, you know, any lymphadenopathy associated with systemic symptoms like fever, night sweats, um, or unintentional weight loss, any lymph nodes that are superclavicular, um, as well as generalized lymphadenopath. Um, so, you know, I find that as really lymphadenopathy present in two or more sites. Um, any lymph nodes that feel either fixed, um, or very firm on exam, any lymph nodes that are greater than 2 centimeters, especially those that seem to be increasing in size from baseline. Um, obviously any, um, lymph nodes, um, associated with an abnormal chest X-ray like a mutasinal mass, um, anything associated with an abnormal CBC which we describe as either the presence of cytopenia, um, in more than one cell line or the association with glass on your CBC, and then Any um lymph node um that is associated with signs of tumor lysis. So, um, anything with the increased LDH increased, um, uric acid as well as any of the increase in those electrolytes that we talked about. And then lastly, thinking about kind of these acute phase reactants and the ESR and CRP, I think any sort of persistent elevation of your acute phase reactions or rising inflammatory markers, especially after, you know, um, Any other underlying infectious ideology that was thought to be contributing to that has sort of passed or resolved, um, should be a referral as well. Um, and then, you know, thinking a little bit, um, you know, about, uh, lymphadenopathy treatment for that, you know, I think it's not uncommon for lymphadenopathy to be treated with, um, you know, a course of antibiotics or, um, um, sort of bacterial-directed, uh, medication, um, especially in a setting of, you know, kind of a known infectious exposure. One thing that we always do sort of, um, Discus, um, you know, and want to caution about is the use of steroids in the setting of lymphadenopathy. It's probably been said many times, um, you know, how we don't recommend using steroids for, um, you know, kind of Undetermined inflammation or, you know, lymphadenopathy of an unclear ideology. And the reason for that really, um, is that steroid treatment is one of the, um, Steroids in general are one of the main classes of medications or chemotherapy that we use for hematological malignancies like leukemia, like lymphoma, as well as other histiocytic diseases like um uh LCH. And so if we use steroids in the upfront treatment without establishing a definitive diagnosis, it unfortunately can mask an underlying malignancy because it's actually used as part of the treatment. Um, and if we use steroids. And then it's determined at a later point um that the lymphadenopathy was actually secondary to a malignant process. You can unfortunately, um, upstage the diagnosis uh for that patient, uh, because we're not sure um if the current disease that we're seeing is already pre-treated or not pre-treated due to the use of steroids, and unfortunately then subjects that patient to a a higher risk form of treatment, which usually includes a longer duration of treatment. Uh, more toxic chemotherapies, and unfortunately, it can also make that patient ineligible for a clinical trial, um, for that particular disease status because they'll be considered pre-treated. And so that's why we harp a lot about, um, you know, establishing a definitive diagnosis before prescribing, uh, steroids before using steroids, particularly in the setting of lymphadenopathy. Um, and so briefly, in the last, um, you know, 5 to 10 minutes before we get into the Q&A portion, I just wanted to talk a little bit about, um, lymphoma in the pediatric, um, and young adult population. And so, um, you know, within pediatrics, we define, um, Uh, we define, uh, lymphoma as a tumor that's derived from abnormal lymphocytes or abnormal white blood cells, and it is along a spectrum with leukemia in that the same underlying um Uh, there is a, uh, sorry, mutation in the same underlying, um, blood cell, which is a white blood cell, um, but the actual sort of manifestation of disease, um, the constitutions of symptoms with leukemia and lymphoma are quite distinct and as we learn more and more about sort of, um, each of these diseases, we're understanding. That there are sort of unique drivers and mutations that sort of separate lymphoma, uh, from leukemia. And so, in general, um, in pediatrics, we just, uh, we categorize lymphoma into sort of two main buckets, one being Hodgkin's lymphoma and the other one being non-Hodgkin's lymphomas. Um, and so, As I mentioned, lymphoma is a tumor derived from lymphocytes. We have two main lymphocytes in our bodies are B cells and our T cells, and similarly, we have sort of B cell-directed lymphoma and T-cell-directed lymphoma. Uh, Hodgkin's lymphoma is a type of B cell lymphoma, uh, in that it derives from our, uh, B cells and our specific immuno phenotypes, uh, like CD 15 and CD30. Positivity that sort of characterize it as a B cell lymphoma. Um, the things that sort of set Hodgkin's lymphoma, um, aside in the sort of unique category, um, is that Hodgkin's in general, spreads in a contiguous manner. Um, so what that mean is, is that if a mutation develops in a cervical lymph node, the next side of disease in Hodgkin's lymphoma will be in a lymph node region next to that neck region. It very rarely could it jump from, you know, sort of from your neck to your groin to your knee. It doesn't really spread in that kind of erratic fashion. It usually spreads in a very sort of contiguous fashion, um, and it rarely involves extranodal sites. So you don't usually typically have involvement of like your spleen. Your liver, um, or your bone marrow. In contrast, non-Hodgkin's lymphoma, which is really quite an umbrella term, uh, for really every other single type of lymphoma, um, is kind of the opposite of this. It can spread noncontiguously, so you can have an abnormal lymph node in your neck, you can. Have an a lymph node in your groin and it just sort of spreads more erratically, and it does usually involve external sites, which can include your GI tract, it can spread to the brain, it can spread to your skin, it can spread to your liver. So, um, those are kind of the two main buckets, um, as I talked about Hodgkin's and non-Hodgkin's. Hodgkin's lymphoma accounts for about 6% of all of our childhood cancers in the US. Um, the incidence is usually age-related and highest among adolescents, um, aged 15 to 19. Um, there are about 33 or 1 million cases per year. Um, of note, as I mentioned, this is particularly in the US in developing countries, there's actually a much higher incidence rate um in childhood, and this is suspected to be due to the EBV, uh, association with Hodgkin's and that being sort of more um endemic, uh, to more developing countries. I think we, Hodgkin's, um, particularly with, uh, lymphoma, has been one of the greatest success cases, and we can now approximately cure about 90 to 95% of children, uh, with Hodgkin's lymphoma. And I'll talk a little bit about sort of how this treatment, um, Treatment for Hodgkin's has um evolved. Uh, thinking about non-Hodgkin's lymphoma, as I mentioned again, this is quite a big umbrella term that includes lymphomas like Burkitt's lymphoma, T lymphoblastic lymphoma, B lymphoblastic lymphoma, really anything else that's not Hodgkin's lymphoma. Um, and so this counts for about 7% of cancers in children younger than 20 in the US. Within the US there's probably about 1200 new cases of the Hodgkin's lymphoma each year. And then in high income countries, more than 80% of children and adolescents, um survive at least 5 years. So as I mentioned, there's a lot more heterogeneity in this group, um, because it comprises a lot of different uh lymphoma processes. Thinking about sort of our treatment approach, um, and staging, um, on the left here, I have a, um, Uh, quick diagram that just um kind of summarizes how we think about Hodgkin's, uh, sorry, not Hodgkin's lymphoma staging in general. Um, and so lymphoma staging can be anywhere from stage one to stage 4. When we think about stage 1 disease, we think about just one sort of region of lymph nodes that are involved, whether that's cervical, axillary. Inguinal mediastinal, but just one group of lymph nodes that are involved. Stage 2 involves two or more lymph node regions that are both on the same side of the diaphragm. So for example, if you have axillary and cervical lymph nodes, that would be stage 2. Stage 3 is two of our lymph node regions that are either that are above and below the diaphragm. So if we had a cervical lymph node involvement and an inguinal because they are on different sides of the diaphragm, that would be considered stage 3. And then stage 4 disease is any disease that extends beyond the lymph nodes. So if you have evidence of disease in your liver, or in your bones, um, or in any other organ, that would be considered stage 4 disease. And so, um, I think, as I mentioned, Hodgkin's has probably been our greatest success story, and we're hoping to make similar progress in the other types of lymphoma that we see in children and young adolescents. And I think there have been a couple of reasons as to why we've made such great progress. I think our contemporary treatment regimen uses a really um nice risk adapted. Um, and kind of response-based treatment stratification. Um, and so based off of, you know, initial symptoms of staging, the presence of, uh, systemic symptoms, the actual bulk or size of the abnormal lymph node itself, we have sort of different, um, treatment stratifications, um, for those individuals, and we're really trying to see. Um, how we can reduce, um, the risk of sort of toxicity and long-term morbidity with the different, um, treatment arms. And so, especially for kids with lower risk disease, which we define as stage 1 or stage 2, as well as some other prognostic factors that we have discovered, we have been really trying to, um, One shorten the duration of exposure to chemotherapy, as well as seeing if we can replace chemotherapy with some of the novel, with some like novel therapies like immunotherapy, um, that don't have that kind of systemic side effects of chemotherapy and don't have the long-term morbidity sort of associated um with chemotherapy. Um, and so, as I mentioned, our current strategies include kind of a multi-agent chemotherapy approach. We are learning a lot more about immunotherapy and really trying to incorporate that upfront in treatment so that we can reduce the amount of chemotherapy that we give. Stem cell transplant. And radiation, which were once uh sort of a standard part of lymphoma treatment are really kind of being delegated or relegated in the relapsed or refractory setting, um, which has really significantly reduced the toxicity and morbidity burden that our patients face. And the last thing I wanted to do was just talk uh um very briefly about, um, you know, how we are really taking into account, um, you know, long term toxicity and morbidity. I think we've achieved such great outcomes, um, recently with all these. Different types of lymphoma, um, treatments, um, that our patients are now living, you know, much longer and healthier lives. And so the next step is really to try to figure out how can we how can we reduce long-term morbidity so that when our patients, you know, Um, cure their cancer, but they're able to live healthy lives without having to worry about all of the side effects from the treatment that they got. And so, one of the sort of now, probably within the past decade, but more recent changes in Hodgkin's lymphoma is our approach to radiation. It used to be that no matter sort of what um stage you were, if you had Hodgkin's lymphoma, you got some Um, some level of radiation, particularly to the chest, because most of Hodgkin's has a lot of mediastinal lymphadenopathy associated with it, and while radiation was a great, um, treatment modality, we found that once our patients sort of survived and were cured of their cancer, they unfortunately, especially our young female adolescent patients had a much higher risk of developing breast cancer later on due to that. Radiation exposure. So, in recognition of this back in 2018, and I think this started even earlier than that, in like 2012 to 2015, we try, we decided, uh, as a group at UCSF to actually eliminate radiation from upfront treatment, um, and use just chemotherapy, uh, for our Hodgkin's patients. And with this sort of analysis, we found Um, uh, we found that we were able to achieve similar outcomes and similar overall survival and disease free survival by omitting radiation, and so, Um, this just kind of summarizes what I just talked about. The main key takeaway is that I think we're constantly thinking about how can we achieve similar outcomes and reduce sort of the long-term toxicity that our patients face, and this was uh quite a great success story, and now pretty much nationally, um, uh, across the US, um, radiation is omitted from upfront treatment so that we can reduce, um, uh, the risk of secondary cancers later on for our patients.
