Lymphoma Overview

1. Lymphoma Overview Timothy S. Fenske, MD April 5th, 2014 Welcome!

2. Topics • What is lymphoma? • What causes lymphoma? • How common is lymphoma? • What are the different types of lymphoma? • Hodgkin vs. non-Hodgkin lymphoma • Staging and how lymphoma affects the body • Brief overview of treatments for lymphoma • How we monitor lymphoma (next presentation) • “Remission” versus “cure”

3. What is lymphoma? • A type of blood cancer which arises from lymphocytes • Can be of B-cell origin or (less commonly) of T-cell origin and rarely of NK cell origin • These cells normally fight viruses, bacteria, fungi and may also kill cancer cells • Lymphocytes normally reside primarily within lymph nodes, blood, bone marrow, and spleen. However to a lesser extent they are found in every organ of the body. • Lymphoma therefore most commonly involves lymph nodes, bone marrow and spleen, but can involve any part of the body. Normal lymphocytes in peripheral blood

4. The Lymphatic System: where the cells of the immune system work and travel • We have a lot of “lymphoid tissue” in our bodies • Lymph nodes are normal • Lymph nodes normally enlarge and become painful with infection • Lymphoma often grows in lymphoid tissues • “nodal”= growing in a lymph node • “extranodal”=growing outside of a lymph node

5. Grand Central Station, New York City (1954)

6. What causes lymphoma? • In most cases, we cannot say • In some cases risk factors can be identified, such as • Immune suppression • HIV, organ / bone marrow transplant • Inherited immune deficiencies • Toxins (agent orange, radiation, prior chemo, firemen) • Infections (H. pylori, EBV, Hep C, HHV-8, HIV) • Autoimmune conditions (RA, lupus, etc) • Underlying condition • Medications (MTX, anti-TNFs, others) • Autoimmune (RA, Sjogren’s, lupus) • In some cases, earlier detection now • Patients living longer due to better treatment for other conditions H. Pylori in stomach biopspy Genetics? Environment? Diet/lifestyle?

7. How does a normal lymphocyte turn into a lymphoma cell ? • Probably involves multiple steps • Chromosome translocations • “Overactivity” of certain signals inside the cell • Cells then either proliferate more than normal, or don’t die when they are supposed to

8. How common is lymphoma? 6th most common cancer 9th leading cause of cancer death

9. How common is lymphoma? Men720,280 Women679,510 Total cancers/yr in US * Excludes basal and squamous cell skin cancers and in situ carcinomas except urinarybladder. Estimated for 2006. American Cancer Society. Cancer Facts & Figures 2006. Atlanta, GA: American Cancer Society; 2006.

10. Overall survival is improving: lots of patients living with lymphoma • 662,789 people living with lymphoma in the US • = Over 12,000 just in Wisconsin • 20,620 people are expected to die from • lymphoma each year www.lls.org (FACTS 2012)

11. 80,321 capacity = 170 lymphoma survivors

12. Who is most likely to be affected by lymphoma? • Hodgkin lymphoma mainly affects those 15-30, but there is a smaller peak in the 60s-70s too • NHL primarily affects those 60 and older but can affect any age Age at diagnosis (y)

13. Non-HodgkinLymphoma International Variation Trends in Incidence, USA • 83% increase in age-adjusted incidence between 1975-2008

14. General approach to patient with lymphoma What does the patient have? DIAGNOSIS How much disease does the patient have? STAGING How will the patient do? PROGNOSIS

15. What does the patient have? DIAGNOSIS

16. How does lymphoma affect the body? • Enlargement of lymph nodes • “B symptoms” • Fevers, drenching night sweats, weight loss • Lowering of blood counts • Pain in some cases • Cough / shortness of breath • Swelling • Rash / itching • GI symptoms • Many others possible: any organ can be affected, although lymph nodes, bone marrow and spleen are most common

17. How does lymphoma affect the body? • There is a very WIDE RANGE of how lymphoma can affect people • In part this is because there are so many types of lymphoma, with variable behavior • However even within one type of lymphoma there is a lot of variation • One end of the spectrum: no symptoms, and discovered “accidently” • Other end: extremely ill, hospitalized, with multiple organs affected

18. What is the difference between Hodgkin and non-Hodgkin lymphoma? HLNHL Subtypes 2 >50 Peak age 20s over age 60 Cases / yr 8,000 70,000 Common sites Neck, mediastinum Various S/Sx Usually mild Often severe 5 yr OS 80+ % Varies Treatment ABVD +/- RT Wide range of options

19. Normal lymph node Benign, “reactive” lymph node Follicular lymphoma Diffuse large B-cell lymphoma

20. Diffuse Large B Cell Lymphoma (Aggressive) In addition to morphology, other special protein stains (immunohistochemistry and flow cytometry) as well as chromosome tests (FISH) or (less commonly) molecular tests (PCR) may be important to establish an accurate diagnosis.

21. Lymphoma in the bone marrow Normal bone marrow Bone marrow involved by lymphoma Paratrabecular aggregates

22. Mantle cell (6%) Burkitt (2.5%) Follicular (25%) Other subtypes (9%) Small lymphocytic (7%) T and NK cell (12%) MALT-type marginal-zone B cell (7.5%) Nodal-type marginal-zone B cell (<2%) Diffuse large B cell (DLBCL) (30%) Lymphoplasmacytic (<2%) There are more than 60 types of lymphoma

23. WM MM ALL MCL, CLL Burkitts, FL, DLBCL Stem cell Pre-B Early B Mature B Activated B Plasmacytoid B Plasma Germinal center • Type of B cell lymphoma depends on: • Where the cell was in development/maturation when it went “bad” • What type of chromosome rearrangement or mutation occurred Why so many lymphomas?

24. WM MM MCL, CLL Burkitts, FL, DLBCL ALL Stem cell Pre-B Early B Mature B Activated B Plasmacytoid B Plasma Germinal center Why so many lymphomas? Just like people, the problem that results depends on the stage of development when things went wrong. How you address these problems will vary . . .

25. Feeling confused?

26. Chaos  Order