Lymphocytosis Flashcards
reactive lymphocytosis
a polyclonal proliferation of T-Cells, almost always due to infection. excess of 4.0<10^9 for absolute lymphocyte count
lymphocyte populations in the blood
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%
neoplastic. lymphocytosis
monoclonal proliferation of B cells 1. chronic lymphocytic leukemia 2. acute lymphoblastic leukemia
reactive lymphocytosis history and physical examination
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
Ddx for findings of reactive lymphocytosis
Differential diagnosis: INFECTIONS: Epstein-Barr virus (mononucleosis) cytomegalovirus (CMV) rubella mumps pertussis infectious hepatitis HIV seroconversion
Symptoms of EBV (cause of reactive lymphocytosis)
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”
investigation/protocols when someone presents with suspected reactive lymphocytosis
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
appearance of atypical lymphocytes
larger than normal lymphocytes, nucleus is more irregular
natural history/prognosis/ complications of reactive lymphocytosis
no complications due to lymphocytosis. prognosis generally excellent with supportive care. repeat blood work when they are feeling better in a few weeks
3 specific infectious illnesses to be wary of when someone presents with reactive lymphocytosis
- pertussis– gram negative bacteria 2. rubella– measels 3. cytomegalovirus (CMV)
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
outline the appraoch to the classification of hematological malignancies (name the myeloid and lymphoid diseases)
outline approach to diagnosis/classification of lymphomas (hodgkin vs non-hodgkin)
most common adult leukemia
CLL. incidence increaes with age
what is CLL
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
what type of appearance of the lymphocytes in classic CLL?
soccer ball lymphocytes. condensed areas of nuclear material
what finding on the PBS would you see with CLL
smudge cells and soccer ball lymphocytes
how does ethnicity play a rolein CLL
seen more in caucasians. also seen more in males.
name the B cell malignancies based on state of b cell maturation
the more mature of the B cell, the less proliferative. the least mature cancer cells are the most aggressive.
which test is required for the diagnosis of CLL?
cytogenetic analysis of peripheral blood or bone marrow.
-immunophenotyping and flow cytometru
outline the APPROACH to the diagnosis of CLL
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
typical phenotypes of B cells in CLL
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”)
general and clinical features of CLL
- 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.
explain the rai and binet staging of CLL
indiciations for CLL treatment.
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)
which antibodies do rituximab and alemtuzumab cover?
why are B cell receptors important to CLL cells?
• 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
benefits and risk to B cell rece3ptor inhibitors
- 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)
____ receptor is overexpressed in CLL and other cancers. what does this do?
how are drugs starting to restore apoptosis in cll cells?
through BCL2 inhibition (venetoclax)
study this diagram:
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
