Heme - Lymphoma 1

Front 1

Reasons to use PCR (3)

Back 1

Establish clonality of T cell receptors

Establish clonality in B cells when cells are surface or cytoplasmic light chain negative.

Detect certain translocations (e.g. t(14;18))

Front 2

Lymphoma risk factors.

Back 2

Age
Immunodeficiency
Autoimmune Disorders

Viral infections: EBV, HIV, HTLV-1, HHV-8, HepC
Bacteria: H Pylori, Chlamydia Psittaci, Borrelia Burgdorferri, Campylobacter jejunei

Environmental/Occupational
Familial

Front 3

Lymph node biopsy

Back 3

Fine needle aspirate isn't good because you need to see the whole node.

Higher elevation in the body, better chance of getting your dx.

Front 4

Clinical presentation of enlarged node

Back 4

Enlarging, painless

Compression - e.g. kidney can't drain so it enlarges.

Fever, night sweats, weight loss.

If marrow infiltrated, can have leukemic component.

Front 5

WHere in spectrum does diffuse large cell lymphoma fall?

Back 5

Intermediate

So sometimes curable, survival is months, and it is aggressive.

Front 6

Tests for staging diffuse large cell lymphoma

Back 6

Specific to this - bilateral bone marrow biopsy

LDH - sign of cell turnover.
CT
Maybe PET (but not routine for follicular lymphomas)
Looking at extranodal sites

Front 7

Staging of lymphoma

Back 7

1 - Single lymph node region or extralymphatic site

2 - Two or more sites on same side of diaphragm.

3 - On both sides of diaphragm

4 - Diffuse involvement of extralymphatic sites with nodal disease. (e.g. BM, bone, organ)

Then add A and B
"B" if you have night sweats, weight loss or fever - worse px.

Front 8

Goal indiffuse large cell lymphoma is always to...

Back 8

CURE!

Front 9

Pathology of diffuse large cell lymphoma

Back 9

Lots of replication of B cells in germinal center and paracortex.

Round/folded nucleus with vesicular chromatin and 1-3 nucleoli.

Nucleus larger than that of a reactive macrophage.

Often a monoclonal light chain pattern and preservation of CD 19 and 20.

Front 10

Bone marrow involvement in diffuse large cell lymphoma is associated with...

Back 10

CNS involvement.

This is important because you need different chemo agents to cross BBB.

Front 11

International prognostic index

Back 11

saw it with diffuse large cell lymphoma

looks at age (>60), performance status (lower is good; 2-4), LDH (elevated), extranodal involvement (>1 site), and stage (3-4).

High IPI is bad - worse px.

Front 13

Tx of diffuse large cell lymphoma

Back 13

High stage (3-4)- Chemo alone with XRT to big disease sites.

Low stage - (1-2) - Combined chemo and XRT to minimize SE of both.

Front 14

R-CHOP

Back 14

Rituxan - anti-CD20 + cyclophosphamide, adriamycin, vincristine, prednisone

Front 15

3 actions of rituxan

Back 15

ADCC, complement-dependent cytotoxicity, apoptosis.

Fc region of it recruits CTLs, complement, and things like that.

Front 16

Epidemiology of diffuse large cell lymphoma

Back 16

most common lymphoid neoplasm.

Goal is cure.

Front 17

Autologous transplantation

Back 17

In people with high IPI scores (bad px), may be good in addition to RCHOP

Front 18

Follicular lymphoma

Back 18

Also a NHL.

Frozen at a stage not replicating, but circulating.

OFten widespread at dx - rarely stage 1 at dx

Currently incurable. (rarely curable with allogeneic stem cell transplant)

GRaded as WHO grade 1,2,3.

1 and 2 is indolent, 3 is aggressive (worse px.

Front 19

Pathology of follicular lymphoma

Back 19

Bcl2 stain - should stain t cells and mantle zone t cells - should be negative. In the follicles in this disease, it is positive.

Predominance of small cleaved lymphocytes. Monotonous accum of a single cell type.

Characteristic immunophenotype
Positive: monoclonal light chain, cd19, cd20, cd10, bcl2
Negative: cd5, cyclin D1/bcl1

ALWAYS TEST FOR CD20 BC OF RITUXAN

Front 20

Genetic abnormality of follicular lymphoma

Back 20

t(14;18)(q32;q31)

bcl-2 expression

Front 21

Grading of follicular lymphoma

Back 21

Based on avg number of large cells in neoplastic follicles. Means more replication and lack of apoptosis.
1 - 0-5
2 - 6-15
3 - More than 15

Front 22

Bcl2

Back 22

Upreg in follicular lymphoma
fusion to ig heavy chain. immortalizes the lymphoma cells.

Front 23

bone marrow biopsy in follicular lymphoma

Back 23

Paratrabecular pattern (rather than normal inter-trabecular pattern)

Front 24

FLIPI score

Back 24

Follicular lymphoma international prognostic index

Looks at age (>60), hemoglobin (<12), more than 4 lymph node sites, stage III/IV, and elev LDH

Front 25

Difference between grade and stage

Back 25

Grade is histology

Stage is where the disease is in the body.

Front 26

Tx of follicular lymphoma

Back 26

Watch and wait
(it may undergo spontaneous improvement/remissions)
early tx does not prolong survival.

If you are going to treat, stage I-IIA is with radiation
IIB - IV is gentle chemotherapy (no hair loss and little n/v)

Rituxan and Zevalin (Rituxan conjugated with radioactive yttrium-90) also seem to be helpful

Front 27

Reasons to treat a follicular lymphoma.

Back 27

painful adenopathy, organ involvement (e.g. kidney swelling), cytopenia due to BM involvement, autoimmune cytopenias (e.g. ITP and hemolytic anemia - these are ESPECIALLY true for follicular lymphomas), very bad B symptoms, high FLIPI score.

Front 28

Transformation of follicular lymphoma

Back 28

2% chance per year.

Transforms to diffuse large cell lymphoma (dx is confirmed with immunologic or molecular tools - the clonality will be the same)

This is more common in grade 3 rather than grade 1

Not more likely to happen if you received aggressive chemo for your follicular lymphoma.

These pts do worse than de novo diffuse large B cell lymphoma pts.

You can give chemo and maybe even autologous BM transplantation.

Front 29

Take home points - General

Back 29

LN biopsy is better than needle aspirate

Cranial LN better than caudal if possible

WHO Classification schemes now take clinical, histology, flow cytometry, cytogenetics into consideration

Front 30

Take home points about diffuse large b cell lymphoma

Back 30

IPI score defines prognosis

Intention of treatment is cure

CHOP + Rituxan

Autologous Transplant for high risk and relapse

Front 31

Take home points about follicular lymphomas

Back 31

Not considered curable

Grade 1/2 are indolent

Grade 3 is aggressive

Bcl-2 blocks apoptosis

FLIPI score defines prognosis

Rituxan significantly prolongs remissions and survival

watchful waiting or treat for selected indications

Can transform into a more aggressive lymphoma