Epidemiology, Etiology, and Risk Factors for Lymphoma

Anthony Mato, MD, MSCE: Hi, my name is Anthony Mato from Memorial Sloan Kettering Cancer Center. I am an expert on chronic lymphocytic leukemia, and I also see some patients with lymphoma. I am joined here by Dr Lori Leslie from the John Theurer Cancer Center, who is a world-renowned expert for patients with lymphomas. Today we’re going to delve deep into the topic of indolent, non-Hodgkin B-cell lymphomas. This is a hot area of research, with lots of new drugs being approved. Hopefully, the days of chemotherapy are soon to be over. We’re going to go through it step by step to provide some information about these new insights. But before we get into the new data, let’s take a step back and try to think about where we are in terms of the diseases, the epidemiology, and the risk factors. If we can go back to the beginning, Lori, can you take us through how non-Hodgkin lymphoma is organized, where the term indolent fits in, and what disorders those most clearly represent?

Lori A. Leslie, MD: Sure. Thank you for that wonderful introduction. I am glad I only see lymphomas because there are almost 100 different types, depending on what criteria you use. There are about 75,000 new cases per year of non-Hodgkin lymphoma, which overall accounts for 85% to 90% of lymphomas, with the other 10% or so being Hodgkin lymphoma. So 75,000 per year may sound pretty common, but overall, that’s only about 5% of all cancers.

When you have non-Hodgkin lymphoma, about 85% are B-cell lymphomas, while the other 15% or so are T-cell lymphomas. Within B-cell lymphoma, you think about how indolent vs aggressive it is, how fast the cells are growing. The most common type within indolent B-cell non-Hodgkin lymphoma is follicular lymphoma, which accounts for about 20% of non-Hodgkin lymphomas, and 1% of all cancers. Although it’s very common in my clinic, it’s not that common in the general oncology clinic.

Marginal zone lymphoma is the second most common, which is about 10% of non-Hodgkin lymphomas, therefore accounting for only about 0.5% of all cancers. Within marginal zone, we’ve got splenic, nodal, and extranodal. Depending on how deeply you go into the subtypes, there are many different types of indolent lymphomas. There is also lymphoplasmacytic lymphoma, a subtype of which is Waldenstrom, then of course our SLL [small lymphocytic lymphoma] and CLL [chronic lymphocytic leukemia] entities. A pretty broad spectrum of types of lymphomas fall into the indolent non-Hodgkin lymphoma group.

Anthony Mato, MD, MSCE: Let’s delve a little more into the risk factors for these diseases. When we see patients in the office, one of the common questions is, “How did this happen to me?” This is one of the areas where we might have some insight into preventable risk factors. I’ll take the follicular component, which there are no known risk factors for that particular disease, and then maybe we can talk together about the marginal zone lymphomas, particularly the extranodal diseases, and what risk factors are known. Gastric marginal zone lymphoma is probably the classic example where we have an antigen-disease relationship. Do you want to give some thoughts about that?

Lori A. Leslie, MD: Yes. I agree with you, that’s one of the most common questions. Having a weak immune system in general is a risk factor for lymphomas across the board. Having a history of lymphomas is a risk factor for other lymphomas. Any state of chronic inflammation can give you increased risk of lymphomas, which is exactly the example you bring up: gastric marginal zone lymphoma is associated with Helicobacter pylori infection. In some situations, eradication of the infection alone can lead to spontaneous regression of the lymphoma, particularly in early disease. There are other chronic infections—hepatitis C, Lyme disease, Campylobacter, Chlamydia psittaci—that can be associated with cutaneous, orbital, pulmonary, and splenic involvement of marginal zone lymphoma. It’s not necessarily part of the guidelines but depending on where they’re from; I always screen for H pylori in patients with gastric marginal zone lymphoma. It certainly can be a targetable potential risk factor for lymphoma, marginal zone lymphoma in particular.

Anthony Mato, MD, MSCE: I agree. There’s evolving literature for infectious organisms that can potentially cause chronic inflammation to lead to these types of lymphomas. We work together and both follow the same mantra where if you can treat the infection, there is the possibility that the lymphoma itself will regress, which is unique about the marginal zone lymphomas. The other thing that we should both comment on is what we see under the microscope. Neither of us are pathologists. We don’t have to get into the details, but the location within the nodal architecture helps to dictate what type of disease we’re dealing with. Are you reviewing your lymph node biopsies? Are there any hints you could give us in terms of distinguishing one type from another?

Lori A. Leslie, MD: One of the key reasons we always review the pathology at Hackensack University Medical Center, which I know you always do at Memorial Sloan Kettering Cancer Center as well, is because there can be some nuances. With follicular, it’s very important to determine how many centrocytes or centroblasts are in the germinal center to tell you whether it’s grade 1/2, which behaves indolently, grade 3b, which we treat like DLBCL [diffuse large B-cell lymphoma], or grade 3a, which can go either way. Sometimes changing between a grade 3a and 3b could significantly change the patient’s treatment plan or even clinical trial eligibility. With marginal zone lymphomas, you can also get fooled relatively easily because it’s characterized by small B cells, but then intermixed are larger B cells. Sometimes it can be challenging for a nonhematopathologist, or even sometimes our hematopathologists, to determine whether it’s a low-grade lymphoma that’s in the process of transforming, a diffuse large B-cell lymphoma, or just a marginal zone lymphoma that’s characterized as having some of those larger cells.

Anthony Mato, MD, MSCE: I concur. I don’t have a lot to add except to say that in addition to the nodal presentations, leukemic phase disease is somewhat common in these disorders as well, so not only are we reviewing the peripheral lymph node biopsies, but it’s also helpful to review the peripheral blood smear and bone marrow pathology.

Transcript Edited for Clarity