Hodgkin's Lymphoma

0:00This is Mayo Clinic Talks, a curated weekly podcast for physicians and health care providers. I'm your host, Darryl Chattga, a general internist at Mayo Clinic in Rochester, Minnesota. Hodgkin's lymphoma is an uncommon but very curable malignancy involving the lymphatic system. It most commonly presents in young adults, but also in those in their mid-50s. Although Hodgkins is generally managed by hematologists or oncologists, the primary care provider plays a major role in its recognition, hopefully leading to a timely diagnosis and eventual staging. What are some early signs of Hodgkins and what preliminary workups should we do prior to referring the patient for a definitive care? How do we monitor those who have had a successful treatment of Hodgkins? These are some of the questions I'll be asking my guest, Dr. Steven Anso, chair of the Division of Hematology,

1:00the Mayo Clinic, as we discuss Hodgkin's lymphoma. You're listening to Mayo Clinic Talks. Steve, welcome, and thank you for joining me today. Darryl, thank you, honored to be here. Well, let's talk about the difference between Hodgkin's lymphoma and non-Hodgkin's lymphoma. Well, Darryl, you're already made an important mention of the fact that it's an uncommon type of lymphoma. It's also one that is often in younger patients. In and of itself, it sort of has a different demographic. But the most important and very different thing is that under the microscope, it has a very different look. Non-Hodgkin lymphoma is of very commonly many cancer cells seen in a kind of a sea of other cells. But Hodgkin lymphoma has just a very small number of malignant cells. The cancer cell in Hodgkin lymphoma is called a Reed Sternberg cell. It has a very unusual kind of large type cell look. But the most important thing is that there is a sea of inflammatory normal cells

2:03that have been attracted and are all around this particular cell. And so it has a very different histological look that really sets it apart. And I guess the one other thing that makes it unusual, we often say that in non-Hodgkin lymphoma, there can be more multiple lymph nodes in many different places. Hodgkin lymphoma sort of seems to move in a kind of a sequential way from one lymph node group to another. And it's often kind of more localized. And I'm sure we'll talk about this. But localized versus more systemic or extensive disease is actually really an important differentiator for Hodgkin lymphoma. And I know that non-Hodgkin lymphoma has a variety of subtypes. Is that true for Hodgkin lymphoma as well? Or is there just basically one type? Well, that's very true. But it's not nearly as extensive as non-Hodgkin lymphoma. There are many different subtypes of non-Hodgkin lymphoma, whereas Hodgkin lymphoma really lands in two groups,

3:05one of which is really being questioned about whether it even is Hodgkin lymphoma. So what I mean by that is we call one group classic or classical Hodgkin lymphoma. And there are some subtypes under that, but probably for a general practitioner, not particularly important. And then there is a different group, which is called lymphocyte predominant Hodgkin lymphoma. And that particular group is a little different. And it's actually more of a B cell malignancy. So I think for a practitioner who doesn't treat this every day, thinking of Hodgkin lymphoma under the umbrella of classic Hodgkin lymphoma, really kind of encompasses most of what we're talking about in one entity. Okay, so what are some of the early symptoms or signs that we should be looking for in a patient who's developed Hodgkin lymphoma? So this is an interesting disease where most typically, patients will notice an enlarging lymph node, often in their neck or in their axilla armpits.

4:06Sometimes they'll notice chest discomfort because the patients may present with a media-stinal mass with a persistent cough or something that really just won't go away. Casional patients can have other symptoms like preritus and itching, really pretty significant, enough that they may even scratch themselves at night because of how itchy they are. And then finally, a really unusual, uncommon, but kind of somewhat weird type of symptoms. And some patients will develop lymph node pain when they drink alcohol. And so they'll just suddenly notice a crushing chest discomfort with a beer and then find that there is a mass in their chest and it turns out to be Hodgkin lymphoma. Well, one of the common things patients come in for an evaluation is an enlarged lymph node. How do we approach a patient who comes in with lymph adenopathy? So I think when it's Hodgkin lymphoma, really important to first of all, be sure that you understand exactly where the lymph nodes are and is this an isolated lymph node

5:06or are there more lymph nodes elsewhere. So we usually recommend a more extensive imaging study. So this would be if you have a lymph node in the neck, a CT that includes the neck and the chest and probably the abdomen as well because you want to be sure that the lymph node site might be restricted to the neck versus more extensive. So that's really, I think, the first step. If you then do see that there is a substantially enlarged lymph node or lymph node group, obtaining a biopsy is again very important and we would then recommend either an excisional biopsy which would need a surgical approach or if it's a complicated thing like in the chest, we recommend a core needle biopsy but with multiple pauses because remember I said the actual cancer cells are rare. Most of it is inflammatory. So there's a bit of a risk that you'll aspirate out just normal cells if you did just in fine needle aspirate. So that's why really important to give the pathologist as much tissue as possible.

6:08And do patients who develop Hodgkin's lymphoma present with a solitary lymph node enlargement or is it more generalized or can be either? Can be either but more typically it tends to be more localized. Often it's just one lymph node group or two adjacent or in close proximity lymph node groups. So for someone may present with neck nodes and then some mediastinal lymph nodes or lymph nodes in the neck, axilla and mediastinum. So often it's more restricted to one space and we actually look specifically whether we can call this limited stage. In other words, one side of the diaphragm versus more advanced stage which would be both sides of the diaphragm. And you mentioned imaging it by CT scan is that the recommended imaging modality? So we would again, if we knew this was Hodgkin lymphoma recommend a CT PET scan. I guess when you're seeing a patient and you haven't made a diagnosis yet, one may not necessarily feel like you want to jump right to a CT PET scan

7:09but we would typically do that as part of the staging evaluation when we do know the patient has Hodgkin lymphoma. I would also say that if you really are suspicious PET scan is also helpful if you do that before you make the diagnosis because clearly biopsying the hottest and brightest FDG avid area would be beneficial, getting the greatest likelihood for a clear diagnosis. Okay, so let's say we have a patient that we suspect has some type of lymphoma, what evaluation should we do prior to referring that patient? So I think as we touched on the things that are most helpful from a practitioner's perspective is to help us make a definitive diagnosis. So imaging study to determine where to get a biopsy and helping have either a surgeon or an interventional radiologist obtain sufficient tissue to call this Hodgkin lymphoma I think is really the most valuable that when we see the patient there are additional testing

8:11that additional evaluation that we will commonly do. The PET scan I mentioned we would use for staging purposes and then in anticipation of treatment we do a number of other additional tests. Those are to check and make sure that the patient's lung function, cardiac function are sufficient to tolerate treatment. So pulmonary function testing, echocardiogram and then kidney and electrolyte and liver function testing as part of ensuring that the patient will be able to tolerate the treatment. You mentioned right at the beginning that patients are often young, many patients are either late teens early adulthood, patients and so we often will talk about fertility and then plan for fertility preservation because the treatments that we would subsequently give may put the patient at some degree of risk for infertility problems in the future. Steve, how important is an urgent referral to hematology or oncology?

9:11So it depends on what you call urgent. This is a disease that moves along steadily but is not hyper aggressive. So it's not a kind of thing where days or weeks necessarily are critical, but I think once the patient has Hodgkin lymphoma getting the patient connected with the hematologist within a few weeks is very appropriate. You will probably not make much difference to patient outcome if the patient is seen in two weeks versus three weeks. So again, I don't think the degree of urgency is immediate. What's much more important is making a definitive clear diagnosis. So I think working steadily to get that in place, most hematologists will accommodate the patient pretty promptly. Is the biopsy the way to make a definitive diagnosis of Hodgkin's versus non-Hodgkin's lymphoma? I think the biopsy is the definitive diagnosis for any kind of lymphoma because guessing is really, I think very detrimental to patients.

10:12We want to be really as 100% sure as we can be. And as I touched on, really important to have enough tissue to make sure that we can actually see, in this case, Hodgkin lymphoma read Sternberg cells. These cells are pretty unique. They have expression of a protein called CD30. And so there is a way for those to be specifically identified and pathologists utilize a combination of a variety of different proteins as a way to pick out the read Sternberg cells from this sea of other inflammatory cells. So let's turn to treatment now. What are the main treatment options available for those with Hodgkins? So first to say treatment options for patients with Hodgkin lymphoma, particularly younger patients, the outcomes are outstanding. I'm talking here with likelihood of being alive and well and having done excellently with treatment in excess of 90% over five years or more. So again, goal here is to provide curative therapy

11:14to patients. And I touched a little earlier on the fact that it's important to know the extent of the disease because limited stage disease where the lymph nodes are clustered in one region, usually on one side of the diaphragm, versus advanced stage disease where there's disease on both sides of the diaphragm. There is a little bit of a difference in how we manage those patients. If you have more limited disease, we can use more abbreviated courses of chemotherapy fewer rounds and utilize our colleagues in radiation oncology in some cases. Versus more advanced stage patients, we will give more treatment, usually in the range of six months of combination chemotherapy and more uncommonly utilize radiation treatment. We talked about the by-mortal presence of this disease, younger individuals and then those in maybe middle age, are the treatments pretty much the same, or do you treat younger patients different than the older ones?

12:14Treatments are very much the same. You mentioned that middle age, but there is actually some really older people who may also have Hodgkin lymphoma and to be frank, those are the patients with the greatest degree of challenge because the young patients in the middle age patients will generally tolerate the treatment that we give very well and will potentially be able to benefit substantially. Really more elderly frail patients, those patients, it may be a lot more challenging. However, in recent days, combination treatments that include what is called an immune checkpoint antibody treatment have really actually made the therapy even more successful and even better tolerated. So we utilize a combination of three chemotherapy drugs plus no volume app, which is a PD1 blocking antibody and that combination actually is quite well tolerated in the older patients, in more frail patients and gives outstanding results. So to say, yes, there are some differences,

13:16but more and more now we're kind of moving to similar treatment with similar outcomes. Steve, you mentioned the excellent prognosis for patients who are younger with Hodgkin's disease. What about the middle age and then the older patient? I assume it's not quite as good. Well, in general, even the middle age patients will have excellent results very similar to the younger patients. The truly old and frail patients, if they could tolerate the same treatment as the younger patients, their outcomes are also excellent. The challenge is just if a patient is really very frail and unable to tolerate the standard treatment, that does jeopardize outcomes to a degraded degree. Also, when you are a lot more old and frail, obviously other illnesses that you may have impact your ability to go through treatment like the next person. The follow-up of many of these patients will be performed by primary care clinicians and are there some things we should watch for just related to treatment that can occur

14:19in some of these patients once they've achieved a remission? Again, very important and I think important to say, practitioners that are partnering with hematologists as patients are either going through treatment or have completed treatment and being followed, they have substantial value in both of those spaces. So while patients are going through treatment, treatment can decrease their immunity and make their neutrophils go low, they are at risk of developing infections. So any problem with an infection or infectious symptoms really needs to be aggressively managed and that patient may present to their general practitioner who can be invaluable in helping manage that problem kind of acutely. There are some unique side effects related to treatment. So for example, ABVD chemotherapy is a very standard. The B is a drug called Bliomycin. Bliomycin can cause some lung toxicity. So if a general practitioner knew the patient was getting Bliomycin and noted a weird cough

15:21or something like that, alerting the hematologist to that would actually be very valuable. Then as we get to sort of done with treatment, there is really, again, a huge role for partnership between the hematologist and the general practitioner for longer term followup, particularly of complications of treatment. So radiation to the chest can put an increased likelihood of cardiovascular complications. Sometimes we're trying to avoid this, but if any radiation hit the breast in a female patient, monitoring for breast cancer risk is really important. And then longer term, any sort of concerns for complications such as abnormal blood counts or something like that where we may have created a myelodesplastic syndrome or some kind of bone marrow failure problem from treatment. These are uncommon, but things we need to watch for. Okay. And how about the long term management of the specific lymphatic disease,

16:22the Hodgkin's once an individual achieves remission, do they ever get a recurrence or is that extremely unlikely? We would love to get to a point where nobody ever has a recurrence, but again, as I mentioned, our benefit these days are into the high 80s, approaching 90% for most patients. There's still unfortunately a subset of patients where this cancer may relapse and return. In those patients, we generally will give additional different chemotherapy and then intensify treatment with what is an autologous stem cell transplant. And commonly after that, use some of the newer drugs, one of them targeting that CD30 protein on the actual Reed Stoneberg cell as additional consolidation for at least six to nine months after the transplant to try and really ensure that we can be done with this whole process. That again has a high likelihood of benefit. And so we're hoping again to increase

17:23the number of people overall that end up being cured. Steve, you mentioned the possibility of secondary malignancies in those who have gone through treatment. Is that purely a result of the treatment or is it related more to the fact that they had Hodgkin's lymphoma? It's actually related to both. So again, one of the reasons one may get Hodgkin lymphoma in the first place is a failure to some degree of one's immune surveillance, your ability to pick up on a cancer. So if you've had one cancer, there is always a risk of a second. Again, not a very high risk, but higher than the average population. So that's where monitoring for that is really important. Our treatments while we're getting better and we're minimizing how much we have to give and we're minimizing the extent of radiation, for example, we're minimizing the number of cycles of chemotherapy. All of that helps for longer term complications, but malignancies caused by either chemotherapy or radiation therapy is still a risk,

18:25not a high one, but one that you have to watch a poor and especially because a sizable population are young and they're gonna have a long life ahead of them where obviously this risk remains over the course of their lives. Well, Steve, you've given us a lot of important information about Hodgkin's lymphoma. Can you summarize our discussion maybe with two or three key points? Yeah, thanks. I think really important is to be cognizant of the fact that enlarging lymph nodes, even in a young patient that looks suspicious, really need a comprehensive evaluation. An imaging study to prove it and a biopsy to make sure that if it is Hodgkin lymphoma, enough tissue is available for the pathologist to really check things through. Second thing I think is to reassure the patient that treatments are very successful with a high likelihood of a very long-term durable remission. Obviously we cannot promise every patient to be cured but our goal is to head toward that and then mitigating long-term toxicities

19:27by anticipating some of them. So for example, making sure that fertility was addressed over and you've got backup options, should the patient have difficulty and then monitoring for cardiovascular problems or second malignancies at a later point? We've been discussing Hodgkin's lymphoma with Dr. Steven Ansel from the Division of Immatology at the Mayo Clinic. Steve, thank you so much for sharing your knowledge with us today. Thanks, Darryl, very grateful to be here. You can now listen to several hundred different medical topics developed for primary care providers on Mayo Clinic Talks Podcasts. Find them at ce.mayo.edu or your favorite podcasting app. If you've enjoyed Mayo Clinic Talks Podcasts, please follow us. We're honored to have you as a listener and invite you to tune in again next week. Stay well.