Lymphocytosis

Question 1

reactive lymphocytosis

Answer 1

a polyclonal proliferation of T-Cells, almost always due to infection. excess of 4.0<10^9 for absolute lymphocyte count

Question 2

lymphocyte populations in the blood

Answer 2

T cells: 60-80%, 70% of them being helper T cells and 30% of the T cell population being CD8+ cells B cells: 10-20% NK cells: 5-10%

Question 3

neoplastic. lymphocytosis

Answer 3

monoclonal proliferation of B cells 1. chronic lymphocytic leukemia 2. acute lymphoblastic leukemia

Question 4

reactive lymphocytosis history and physical examination

Answer 4

Reactive Lymphocytosis History: Consistent with viral infection  fever, chills, night sweats  cough (non-productive), sore throat  headache, muscle aches  general malaise-loss of appetite  photophobia  rash Physical Examination: the patient may have:  pharyngitis  meningismus  rash  jaundice  Lymphadenopathy (tender)  hepatomegaly/splenomegaly  shortness of breath

Question 5

Ddx for findings of reactive lymphocytosis

Answer 5

Differential diagnosis:  INFECTIONS:  Epstein-Barr virus (mononucleosis)  cytomegalovirus (CMV)  rubella  mumps  pertussis  infectious hepatitis  HIV seroconversion

Question 6

Symptoms of EBV (cause of reactive lymphocytosis)

Answer 6

Fever  Tender lymph nodes  Fatigue – often extended duration  May have palpable splenomegaly  May have hepatitis  Typical age – teens/20s  Not necessarily aware of “sick contacts”

Question 7

investigation/protocols when someone presents with suspected reactive lymphocytosis

Answer 7

Investigations: A neoplastic cause must be excluded. Differentiating factors include:  History - eg time frame - symptoms not improving (fever, fatigue; pallor)  Physical exam: large organomegaly (if splenomeagly, maybe EBV)? or lymphadenopathy, petechiae  Lab - blood smear - atypical lymphocytes vs. blast cells  flow cytometry: polyclonal increase in T-cells  NB: complete blood count and differential -bone marrow examination not usually needed

Question 8

appearance of atypical lymphocytes

Answer 8

larger than normal lymphocytes, nucleus is more irregular

Question 9

natural history/prognosis/ complications of reactive lymphocytosis

Answer 9

no complications due to lymphocytosis. prognosis generally excellent with supportive care. repeat blood work when they are feeling better in a few weeks

Question 10

3 specific infectious illnesses to be wary of when someone presents with reactive lymphocytosis

Answer 10

1. pertussis– gram negative bacteria 2. rubella– measels 3. cytomegalovirus (CMV)

Question 11

Summary to reactive lymphocytosis

Summary: 1. Reactive lymphocytosis is usually due to infection 2. History/physical exam most important to distinguish
from neoplastic cause 3. Laboratory investigations show a polyclonal
lymphocytosis 4. Prognosis generally very good with supportive
measures 5. Most simple solution is to repeat blood work when they
are feeling better in a few weeks

Question 12

outline the appraoch to the classification of hematological malignancies (name the myeloid and lymphoid diseases)

Answer 12

Question 13

outline approach to diagnosis/classification of lymphomas (hodgkin vs non-hodgkin)

Answer 13

Question 14

most common adult leukemia

Answer 14

CLL. incidence increaes with age

Question 15

what is CLL

Answer 15

A neoplastic disease characterized by the
clonal proliferation and accumulation of small,
mature –appearing immunologically
incompetentB lymphocytes in the blood,
marrow, lymph nodes and spleen

Question 16

what type of appearance of the lymphocytes in classic CLL?

Answer 16

soccer ball lymphocytes. condensed areas of nuclear material

Question 17

what finding on the PBS would you see with CLL

Answer 17

smudge cells and soccer ball lymphocytes

Question 18

how does ethnicity play a rolein CLL

Answer 18

seen more in caucasians. also seen more in males.

Question 19

name the B cell malignancies based on state of b cell maturation

Answer 19

the more mature of the B cell, the less proliferative. the least mature cancer cells are the most aggressive.

Question 20

which test is required for the diagnosis of CLL?

Answer 20

cytogenetic analysis of peripheral blood or bone marrow.

-immunophenotyping and flow cytometru

Question 21

outline the APPROACH to the diagnosis of CLL

Answer 21

Diagnosis
– History

– Physical exam

– Bloodwork
• CBC, flow cytometry, immunoglobulins, chemistry – Lymph node biopsy

• If lymphoma is high on differential diagnosis – Bone marrow aspiration and biopsy
• Not usually required

Question 22

typical phenotypes of B cells in CLL

Answer 22

CD5+, CD19+, CD23+, DimCD20, Dim Surface Lg

Minimum needed to confirm diagnosis is
≥ 5 x 109/L B lymphocytes in peripheral blood for ≥ 3
months1 (if less, called “monoclonal B cell lymphocytosis”)

Question 24

general and clinical features of CLL

Answer 24

• 25% are asymptomatic when caught. some may have some weight loss.
• minimal lymphaenopathy or unexplained lymphocytosis.
• possible systemic symptoms of weight loss, recurrent infections (particularly encapsulated organisms Streptococcus pnemoniae, Klebsiella pneumonia, group B streptococci, Escherichia coli, Neisseria meningitides and Haemophilus influenzae), bleeding or fatigue/shortness of breath
• clinical features:
• lymphadenopathy (non tender, asymptomatic)
• organomegaly (splenomegaly due to leukemic cell infiltrate, can cause cytopenia)
• cytopenias including anemia and thrombocytopenia due to splenic sequestration, autoimmune, or marrow infiltration.

Question 25

explain the rai and binet staging of CLL

Answer 25

Question 26

indiciations for CLL treatment.

Answer 26

most of them are “watch and wait” cases, there is no evidence that early treatmnet prolongs survival in these patients.

when to treat:

Lymphocyte doubling time of less than 6
months • Systemic symptoms • Symptomatic lymphadenopathy or
splenomegaly • Significant anemia (Hgb <110) or
thrombocytopenia (platelets <100)
– From bone marrow involvement – Autoimmune

You don’t need to treat in the early stages with the exception being patients with a rapid diseas eprogression (lymphocyte doubling time less than 6 months)

Question 28

which antibodies do rituximab and alemtuzumab cover?

Answer 28

Question 29

why are B cell receptors important to CLL cells?

Answer 29

• The B-cell receptor is an
immunoglobulin (Ig) receptor on
CLL cells – activated BCR is
essential for CLL cell survival

• BCR signalling is enhanced in cells
with unmutated IgV H
• Microbial or autoantigens bind
BCR, causing phosphorylation

• Phosphorylation induces survival
signals via downstream kinases

• we need to inhibit the B cell receptor

Question 30

benefits and risk to B cell rece3ptor inhibitors

Answer 30

• Oral agents • No significant myelosuppression
• Continued until progression (? compliance)

• Unusual side effects (colitis from idelalisib, atrial
fibrillation from ibrutinib)
• Interestingly, no benefit to addition of rituximab
to ibrutinib in CLL (so value of anti-CD20 mAbs
with novel agents unclear)

Question 31

____ receptor is overexpressed in CLL and other cancers. what does this do?

Answer 31

Question 32

how are drugs starting to restore apoptosis in cll cells?

Answer 32

through BCL2 inhibition (venetoclax)

Question 33

study this diagram:

Question 34

Note:

Many patients are treated with watchful-waiting
– When treatment is required, it is used to control symptoms
(lymphadenopathy/cytopenias) – The only known curative treatment is stem cell transplant (and
possibly highly intensive chemo in very young patients) (ie most
patients will experience relapse(s) and re-treatment