Lymphoma Overview

Timothy S. Fenske, MD

April 5th, 2014

Welcome!

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”

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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

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

Grand Central Station, New York City (1954)

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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?

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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

How common is lymphoma?

6th most common cancer9th leading cause of cancer death

How common is lymphoma?

Prostate 33%

Lung and bronchus 13%

Colon and rectum 10%

Urinary bladder 6%

Melanoma of the skin 5%

Non-Hodgkin’s lymphoma 4%

Kidney 3%

Oral cavity and pharynx 3%

Leukemia 3%

Pancreas 2%

All other sites 18%

Women679,510

Men720,280

31% Breast

12% Lung and bronchus

11% Colon and rectum

6% Uterine corpus

4% Non-Hodgkin’s lymphoma

4% Melanoma of the skin

3% Thyroid

3% Ovary

2% Urinary bladder

2% Pancreas

22% All other sites

* 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.

Total cancers/yr in US

Overall survival is improving: lots of patients living with lymphoma

www.lls.org (FACTS 2012)

• 662,789 people living with lymphoma in the US

= Over 12,000 just in Wisconsin

• 20,620 people are expected to die fromlymphoma each year

80,321 capacity = 170 lymphoma survivors

Age at diagnosis (y)

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

Non-Hodgkin Lymphoma

Trends in Incidence, USA International Variation

•83% increase in age-adjusted incidence between 1975-2008

General approach to patient with lymphoma

What does the patient have?

How much disease does the patient have?

How will the patient do?

DIAGNOSIS

STAGING

PROGNOSIS

What does the patient have?

DIAGNOSIS

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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

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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

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What is the difference between Hodgkin and non-Hodgkin lymphoma?

HL NHL

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

Follicular lymphoma Diffuse large B-cell lymphoma

Benign, “reactive” lymph nodeNormal lymph node

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.

Bone marrow involved by lymphomaNormal bone marrow

Lymphoma in the bone marrow

Paratrabecular aggregates

There are more than 60 types of lymphoma

T and NK cell(12%)

Other subtypes(9%)

Burkitt(2.5%)

Mantle cell(6%)

Diffuse large B cell

(DLBCL)(30%)

Follicular(25%)

Small lymphocytic(7%)

MALT-type marginal-zone

B cell (7.5%)

Nodal-type marginal-zone

B cell (<2%)

Lymphoplasmacytic (<2%)

Why so many lymphomas?

Pre-B Early B Mature B Plasmacytoid B

Type of B cell lymphoma depends on:

1) Where the cell was in development/maturation when it went “bad”

2) What type of chromosome rearrangement or mutation occurred

PlasmaActivated BStem cell

Burkitts, FL, DLBCL WM MMMCL, CLLALL

Germinal center

Why so many lymphomas?

Pre-B Early B Mature B Plasmacytoid BPlasmaActivated BStem cell

Burkitts, FL, DLBCL WM MMMCL, CLLALL

Germinal center

Just like people, the problem that results depends on the stage of development when things went wrong.

How you address these problems will vary . . .

Feeling confused?

Chaos Order