6a- Lymphocytosis and Lymphoid Leukemias Flashcards
Match the slides (A and B) with the correct clinical and pahtologic findings
Clinical
- 16 y/o with cervical adenopathy and sore throat
- 64 y/o with diffuse adenopathy and weight loss
Pahtologic
- immunophenotypically abnormal, monoclonal B or T cells
- immunophenotypically normal, polyclonal B or T cells
A is a 64 yr old with diffuse adenopathy and weight loss, and immunophenotypically abnormal, monoclonal B or T cells **indicates leukemic process**
B is a 16 yr old with cervical adenopathy and sore throat and and immunophenotypically normal polyclonal B or T cells **probably have mono bc these are polyclonal reactive lymphocytes**
What is absolute lymphocytosis and what 5 findings are important to consider when deciding whether the lymphocytes are simply reactive, or neoplastic?
lymphocyte count of over 4,000/uL
Duration: Short=reactive, long=neoplastic
Morphology: polyclonal=reactive, monoclonal=neoplastic
Absolute Lymphocyte Count: ~4,000=reactive, ~60,000=neoplastic
Associated clinical findings
Flow findings
What are 7 examples of benign/non-clonal lymphocytosis?
**these are common in peds/adolescents
Infectious-mononucleosis
IM-like syndromes (common): CMV, Adeno< Acute HIV, Toxo
Other viuses: Hepatitis, Chicken pox
Tuberculosis
Transient stress lymphocytoses (common, ie after an MI or trauma)
Whooping cough
Polyclonal B-cell lymphocytosis: super rare no need to learn this one!
What are 6 examples of neoplastic/clonal lymphocytosis?
**she emphasized that we know these <3
Chronic Lymphocytic Leukemia (CLL)
Leukemic Lymphoma
Sezary Syndrome
Hairy Cell Leukemia
Adult T-Cell Leukemia
T-Cell Large Granular Lymphocytic Leukemia
What are the clinical findings (population, duration, symptoms) of Infectious Mononucleosis and what virus usually causes it?
Clinical:
- Acute, self limited
- older children, adolescents
- fever, fatigue, sore throat, lymphadenopathy, possibly hepatosplenomegaly
***Ebstein Barr Virus
how do we diagnose Infectious Mononucleosis (IM)
>50% of the differential are mononuclear cells
heterogenous lymphocyte morphology (bc homo would be neoplasm)
>10% of white cells are reactive lymphocytes (sometimes referred to as atypical lymphs)
What is the metodology used to assess clonality in B cells? How about in T/NK Cells?
B cells:
- light chain restriction on cell surface (Kapps vs lambda) by flow cytometry or immunohistochemistry
- IgH variable gene PCR
- Immunophenotypic abberancy (ie. CD5 on B cells)
T/NK
- TCR gene PCR
- Immunophenotypic abberancy
Please identify the following cells
A: Eosinophil
B: BLAST! Immature
C: mature lymphocyte
D: Neutrophil
What ancillary study do we use to determine whether an immature/blast cell is myeloid vs lymphoid?
Flow cytometry!
Are ALLs usuallyinvolve B cells or T cells
B cells
How do we determine if something is an acute leukemia? Where in the body does it occur? What are the 2 categories?
>20% blasts in the bone or marrow (although may involve extramedullary sites too! ie other than BM, could be spleen!)
2 categories: Myeloid (AML) vs. Lymphoid (ALL)
How do we differenciate between AML and ALL? (i what would the flow cytometry show us)
By morphology: Myeoloblasts have Auer Rods (also myeloblasts have more cytoplasm but thats beyond our scope)
By Immunophenotype:
- Myeloid: CD13, 14, 33, 117
- Lymphoid: CD3, CD19, CD20
**Quick review from past decks**
What age group typically gets AML?
What morphology is commonly seen?
What is the significance of Myelodysplasia?
What are the 4 classifications?
Adults>children
Myeloblasts may have Auer Rods, may have granulocytic, erythroid, megakaryocyte, monocytic differentiation
Myelodysplasia (MDS)=pre-leukemia
Classifications:
- AML w/ recurrent cytogenetic abnormalities
- AML w/ myelodysplasia-associated changes
- AML/MDS, therapy related
- AML, NOS
WHat age group typically gets ALL? What cells are present? Is there a preleukemia state like in AML?
childre>adults
lymphoblasta
No pre-leukemia state ! AML has Myelodysplasia. but ALL doesn’t have that
What are the 2 classifications of ALL and what translocations are associated with each? Also how does the prognosis relate to the translocations?
B cell ALLs (85%)
- t(12;21) most common in kids
- t(9;22) poor prognosis
T cell ALL (15%)
- adolescent males w/ mediastinal masses
- worse prognosis
What are 3 mature B cells markers? 3 immature markers?
B cell markers:
- CD19(+)
- CD22(+)
- CD20(+/-)
Immature markers:
- TDT(+)
- CD34(+)
- CD10(+) (sometimes)
What are the 5 things to consider when determining prognosis for B-ALL (B cell ALL)?
Age
Cytogenetics
WBC Count
CSF involvement
Marrow involvement following therapy
What are 3 good prognostic indicators in B-ALL
age 2-10 y/o
hyperdiploidy (>50 chromosomes)
t(12;21)
What are 6 BAD prognostic indicators in B-ALL?
less than 2 y/o or older than 10
t(9;22), MLL gene
Hypodiploidy (<45 chromosomes)
elevated WBC count (>100,000/uL)
CSF involvement
marrow involvement at day 15
How do T-ALLs apear morphologically/ what do we find on flow cytometry?
How do they often present?
Meadiastinal masses in adolescents “thymic lymphomas”
May appear morphologically identical to B-ALL but flow cytometry shows: CD3(+), CD1a(+)
What are the 4 options for treatment of all cancers?
(all, not acute lymphoid leukemia (ALL))
Chemotherapy
Targeted therapy: tyrosine kinase inhibitors
Cellular therapy: Stem cell transplant, CAR-T Cells
Immunotherapy: Inotuzumab, Blinatumimab
How do we treat ALL?
Induction
Intensification
CNS Prophylaxis (bc chemo doesnt reach testes or brain)
Maintenance (can be years)
**often almost 3 yrs of treatment, but only 6 months intense
WHat are 3 hip new drugs that have drastically improved the survival for ALL?
Inotuzumab Ozogamicin
Blinatumomab (Bring the leukemia cells and your T cells together for better fighting)
Dasatinib-1st line for adults with philadelphia chromosome ALL
For a patient with CLL compare the immunophenoytype of the lymphocytes in the lymph, spleen and peripheral blood. What is a better diagnositic test flow cytometry or biopsy?
They are all the same! monoclonal! wooooooo!
Flow cytometry bc biopsy is invasive
How do people describe the appearance of CLL cells?
Soccer ball chromatin
What is the most likely immunophenotype of the lymphocytes in CLL? Is CLL indolent or aggressive?
CD5(+), CD20(+), CD23(+) cells expressing kappa light chains only
*only kappa light chains bc monoclonal, could also be only gamma light chains
CLL is indolent!
Why would a person with CLL be anemic (hgb 8g/dL), have lymphocytosis (140k/uL), and have a low reticulocyte count? 0.015 * 10^6/uL
the bone marrow was completely replaced by neoplastic cells so they aren’t making any reticulocytes and the lymphocytes are spilling out of the bone marrow into the peripheral blood
What is the most common leukemia in the western world? What type of cells does it involve? What is the mean age? How do they present? and is it indolent or aggressive?
Chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL)
Neoplasm of mature B cells, mean age of diagnosis=65 y/o
presentation: aysmptomatic or lymphadenopathy
indolent, but 2-8% may transform to aggressive B-cell lymphoma (Richter syndrome)
CLL/SLL is a leukemia and a lymphoma. What is the significance of this?
It can involve the blood and bone marrow (leukemia) and lymph (lymphoma)
Involving the lymph means
- tissue based
- lymph nodes, spleen, MALT
What does CLL/SLL look like as a lymphoma?
Has proliferation centers
- pale, ill-defined nodules
- prolymphocytes admixed with small lymphocytes with pale cytoplasm
**We don’t need to recognize the picture, we just need to know abou the proliferation centers
If a small B cell leukemia/lymphoma is CD5+ what 2 things could it be?
What if it was CD5-, what 2 things could it be?
Small B cell leukemia/lymphoma that is….
CD5+: Mantle cell lymphoma or CLL/SLL
CD5-: Follicular lymphoma or marginal zone lymphoma
What is the diagnosis if you have a small B cell leukemia/lymphoma that is
CD5+, CD23-, FMC7+
Mantle cell lymphoma
What is the diagnosis if you have a small B cell leukemia/lymphoma that is
CD5+, CD23+, FMC7-
CLL/SLL
What is the diagnosis if you have a small B cell leukemia/lymphoma that is
CD5-, CD10+
Follicular lymphoma
What is the diagnosis if you have a small B cell leukemia/lymphoma that is
CD5-, CD10-
MALT lymphoma
What are 3 good prognostic factors for CLL/SLL?
Low Rai stage
mutated IGHV gene
Deletion 13q
What are 4 bad prognostic factors for CLL/SLL
High Rai stage
unmutated IGHV gene
CD38/ZAP-70 expression
Deletion 11q, 17p
How do we determine which Rai stage someone is?
stage 0= lymphocytosis
stage I= Lymphocytosis, adenopathy
stage II= Lymphocytosis, adenopathy, and organomegaly
stage III= lymphocytosis, adenopathy, organomegaly, anemia
stage IV= lymphocytosis, adenopathy, organomegaly, anemia, thrombocytopenia
How doe the prognosis change for CLL based on the Rai stage?
Stage 0- 150 months
stage I- 101 months
stage II- 71 months
stage III/IV- 9 months
What are the lab parameters that indicate treatment of CLL? How about Clinical parameters?
Lab
- Rapid lymphocytic doubling itme (< 6months)
- Hgb < 10g/dL
- Platelets <100,000/uL
Clinical
- Autoimmune anemia or thrombocytopenia
- Richter transformation (large cell transformation)
- Enlargins symptomatic lymph nodes
- B symptoms
What do we worry that CLL may progress to?
B cell lymphoma, (Richter syndrome)
