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
