Leukemia Clinical Cases Flashcards
You see the HE below…
what is the typical age of the patient presenting with this?
Is this Immunophenotypically normal, polyclonal B cells
OR
Immunophenotypically abnormal, monocloncal B cells
Mononucleosis; more common in teens and young adults
Immunophenotypically normal, polyclonal B cells
What symptoms are typical of mononucleosis?
Splenomegaly d/t toxic T cells reacting to B cells,
hepatomegaly
fatigue and fever
Your pathologist attending points out the gingersnap apperance of the cells in the smear. What is the disease and what patient population is this typically seen in ?
Chronic Lymphocytic leukemia
seen in elderly
Your patient has been diagnosed with CLL, what is the pathology?
immunophenotypically normal, polyclonal B cells
OR
Immunophenotypically abnormal, monoclonal B cells?
Immunophenotypically abnormal, monoclonal B cells
The following are all examples of:
– Infectious mononucleosis
– IM-like syndromes
(common)
• CMV, Adeno, Acute HIV,Toxo
– Other viruses
• Hepatitis, chickenpox
– Tuberculosis
– Transient stresslymphocytosis (common)
– Whooping cough
– Polyclonal B-ce
Benign non-clonal lymphocytosis
The following are all examples of:
– Chronic lymphocyticleukemia (CLL)
– Leukemic lymphoma
– Sezary syndrome
– Hairy cell leukemia
– Adult T-cell leukemia
– T-cell large granular
lymphocytic leukemia
Neoplastic/clonal lymphocytosis
What clonality assesment methodology do we use for B cells?
• Light chain restriction on cell surface(kappa v lambda) by flow cytometry or
immunohistochemistry
• IgH variable gene PCR
• Immunophenotypic aberrancy (ie. CD5 expression on B cells)
What clonality assesment methodology do we use for T cells?
- T cell receptor gene PCR
- Immunophenotypic aberrancy
What percentages of Lymphoblast leukemias are repreasented by B cells and T cells
A 29 yo male teacher has increasing SOB while jogging and fatigue for past 3 weeks.
Afebrile, no change in weight/loss of appetite/muscle aches/sweats/bruising
PE he looks healthy, no rashes
Labs: 11.3/mL WBC
HgB = 6.3 and hematocrit = 19
MVC = 100 and plats = 115,000
has abnormal WBC smear w/ over 60% of cells like this.
What do the cells represent and what other tests should we get to Dx patient?
immature lymphoblasts–shoudn’t have that many in blood.. over 20% is concerning
Do flow cytometry to get more info! we cannot at this point give definitive Dx nor say what they will mature into
In Acute leukemia:
- _____blasts in the blood or bone marrow
- May involve extramedullary sites too
- Initially classified into two categories:
≥20%
– Myeloid (AML) vs. Lymphoid (ALL)
Acute leukemia is diagnosed based on morphology and immunophenotype
we see
CD13, 14, 15, 33, 117 and Auer rods in what type of Acute Leukemia?
In Myeloid leukemia
These markers are present in what type of acute leukemia?
CD3, CD19, CD20
Acute lymphoid leukemia
Which picture below is a mature and which is the immature cell?
Blasts or immature cells are on the right
Mature cells are on the left
Flow cytometry reveals 60% population of large cells are positive for CD10, CD19 and CD34 and NEGATIVE for CD3 and CD20
Where in the body where we also see these cells?
Cerebrospinal fluid, Lymph nodes, Bone marrow and splenic sinusoids
This is B-ALL and we see very dispersed invovement
In a patient will B-ALL would we see:
expanded myeloid lineage
majority of cells showing MPO expression
Cells with cytogenic abnormalities
Cells with cytogenic abnormalities
–this is seen in all ALLs
You see these resuts on a cytogenetic analysis from patient with B-ALL. What is true of these test results?
Hyperdiploidy
This is FAVORABLE for patient!!!
Patient presents with large mediastinal mass, if this is neoplastic, what type of tumor cells would we expect to see?
CD3+
AML is seen in adults or children
has what cell features?
If we see myleodysplasia, what do we call it?
Adults > Children
• Myeloblasts ± Auer rods
– May have granulocytic, erythroid, megakaryocytic, monocytic differentiation
• Myelodysplasia = pre-leukemia
ALL is seen in children or adults?
Does or does not have pre-leukemia state?
HOw is it classified?
Children
no pre-leukemia state
85% B cells
15% T cells
What is the most common cytogenetic abnormality in child with B cell ALL?
Is this a good or bad prognosis?
t(12;21)
good prognosis
What is the cyogenetic results is the worst prognosis in child with B cell ALL?
t(9;22)
T-ALLs are seen in what type of patient and how does it present?
young male adolescent
mediastinal mass
worse ALL prognosis
What are the key prognostic factors in B-ALL?
- Age
- Cytogenetics
- White blood cell count
- CSF involvement
- Marrow involvement following therapy
What are the 6 bad signs for B-ALL?
– <2y/o, >10y/o
– t(9;22), MLL gene
– Hypodiploidy (<45chromosomes)
– Elevated WBC count (>100k/uL)
– CSF involvement
– Marrow involvement at day 15 post chemo
What are the three Good prognostic indicators for B-ALL?
– 2-10y/o
– Hyperdiploidy (>50 chromosomes)
– t(12;21)
T-ALL
•______ masses in adolescents
– “thymic lymphomas”
• May appear morphologically_____ to B-ALL
– Flow cytometry:
Mediastinal
identical
CD3(+), CD1a(+)
What are the 4 stages in ALL treatement?
- INDUCTION
- INTENSIFICATION
- CNS PROPHYLAXIS
- MAINTENANCE
What is Blinatumoamb and what is it used for?
bispecific T-cell engaging (BiTE®)
antibody construct that directs cytotoxic T-cells to
CD19 expressing B-cells.
(Chimeric antigen receptors for the adoptive T cell
therapy of hematologic malignancies)
What is the first line TX for adult patients with Ph+ chromosome ALL
Dasatinib; tyrosine kinase inhibitor~ take pill every day
65 yo female has increased fatigue for 6mo and LUQ, decreased appetite.
Healthy appearing, but you know several firm, mobile lymph nodes about 1.5 cm in posterior triangles.
Tip of spleen is palpable
WBC = 60,000
90% differential lymphocytes, 8% neutrophils, 2% eosinophils
HgB = 12 and plats = 170,000
which of following is most likley true:
Pierpheral blood lymphocytes are most likely T cells
Peripheral blood lymphocytes have same immunophernotype as those in the lymph nodes and spleen
EVB serology indicates recent infection
Peripheral blood lymphocytes have same immunophernotype as those in the lymph nodes and spleen
WBC = 60,000
90% differential lymphocytes, 8% neutrophils, 2% eosinophils
What is the absolute lymphocytes count in this case?
54,000
If you see a peripheral smear with gingersnap cells, what is the Dx?
What CD markers do you expect?
would this be kappa expressing, lamba expressing or both
CLL (may be asymptomatic)
CD5+, CD19+, CD23+ and cells express kappa light chain only is more common
If a patient has CLL and the oncologist recommends a ‘watch and wait’ approach, what is true about this type?
this is INDOLENT
Pt was dx with CLL 9 months ago with a ‘watch and wait’ approach suggested. She now has progressive anemia (hgb = 8) and lymphocyosis (140k/uL) with night sweats and fever. Why is this going on?
Bone Marrow replaced with neoplastic cells
If you have patient with 17p deletion that has CLL, what is the significance?
very bad prognostic indicator!
17p deletion is assoicated with loss of p53
Why do we see splenomegaly in hairy cell leukemia
dt red pulp inflitration
Hairy cell leukemia:
what population of people?
______cells
associated with fibrosis in marrow called:
40-60 yo males
TRAP+ cells
dry tap
What would our flow dx be of Hairy cell leukemia?
bright CD11c and CD22 expression
(indolent)
Mantle Cell lymphoma and CLL/SLL both have what CD marker?
How are they different?
Both have CD5+
Mantle Cell lymphoma = CD23- and FMC7+
CLL/SLL = CD23+ and FMC7-
Follicular lymphoma and marginal zone lymphoma are the same and different in CD markers how?
BOTH are CD5-
Follicular lymphoma = CD10+
MALT lymphoma = CD10-
What are four bad prognostic indicators for CLL/SLL?
– High Rai stage
– Unmutated IGHV gene
– CD38/ZAP-70 expression
– Deletion 11q, 17p
What are 3 Good prognostic indicators in CLL/SLL?
– Low Rai stage
– Mutated IGHV gene
– Deletion 13q
What is the prognostic staging system for CLL?
Stage 0 — 150 months
Stage I — 101 months
Stage II — 71 months
Stages III/IV — 9 months
What are the lab indication to tx in CLL?
Rapid lymphocyte doubling time (<6months)
if hemoglobin is below 10
if plats below 100k
What are clincal indications for treatement in pt with CLL?
Autoimmune anemia or thrombocyopenia
Richter transformation (large cell transformation)
Enlarging symptomatic lymph nodes
B symptoms
What drug therapy would we give to symptomatic patient with CLL?
Rituximab
and cyclophosphamide
*95% of patients will respond, this is not cure, just tx
What are the bad cytogenetic prognosis for CLL?
17p
What are the not so bad cytogenetic prognosis for CLL?
del (13q)
Mutated IgHV
(intermediate = trisomy 12)
what signaling is overacting in CLL?
B cell signaling: the Pl3k adn BTK) signaling motif
***to cure, give pts Pl3 kinase inhibitor!!! see much improved results
Sezary Syndrome triad
Triad: erythroderma, generalized
lymphadenopathy, circulating sezary cells
• “Cerebriform nuclei” and CD4 + T cells
seen in:
Sezary Sydnrome
(think cerebriform = brains~~ what patients faces look like)
What is our concern with Sezary and MF?
that it will transform into aggressive T cell tumor
What disease do we see flower cells in?
Adult T-cell leukemia/lymphoma
HTLV-1 associated! most infection DO NOT devo ATLL
CD4(+) Tcell neoplasm, seen in Japan/Caribean/Africa
HYPERcalcemia and aggressive
Adult Tcell leukemia/lymphoma
- Lymphoproliferative disorder of cytotoxic T cells
- Indolent disorder
- Usually presents with neutropenia, anemia and splenomegaly
- Associated with autoimmune disorder (rheumatoid arthritis)
Large granular lyphocytic leukemia
What characterstics are presented in large granular lymphocytic leukemia?
Neutropenia, and anemia and splenomegaly
