6a- Lymphocytosis and Lymphoid Leukemias Flashcards

1
Q

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

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**

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2
Q

What is absolute lymphocytosis and what 5 findings are important to consider when deciding whether the lymphocytes are simply reactive, or neoplastic?

A

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

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3
Q

What are 7 examples of benign/non-clonal lymphocytosis?

**these are common in peds/adolescents

A

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!

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4
Q

What are 6 examples of neoplastic/clonal lymphocytosis?

**she emphasized that we know these <3

A

Chronic Lymphocytic Leukemia (CLL)

Leukemic Lymphoma

Sezary Syndrome

Hairy Cell Leukemia

Adult T-Cell Leukemia

T-Cell Large Granular Lymphocytic Leukemia

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5
Q

What are the clinical findings (population, duration, symptoms) of Infectious Mononucleosis and what virus usually causes it?

A

Clinical:

  • Acute, self limited
  • older children, adolescents
  • fever, fatigue, sore throat, lymphadenopathy, possibly hepatosplenomegaly

***Ebstein Barr Virus

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6
Q

how do we diagnose Infectious Mononucleosis (IM)

A

>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)

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7
Q

What is the metodology used to assess clonality in B cells? How about in T/NK Cells?

A

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
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8
Q

Please identify the following cells

A

A: Eosinophil

B: BLAST! Immature

C: mature lymphocyte

D: Neutrophil

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9
Q

What ancillary study do we use to determine whether an immature/blast cell is myeloid vs lymphoid?

A

Flow cytometry!

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10
Q

Are ALLs usuallyinvolve B cells or T cells

A

B cells

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11
Q

How do we determine if something is an acute leukemia? Where in the body does it occur? What are the 2 categories?

A

>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)

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12
Q

How do we differenciate between AML and ALL? (i what would the flow cytometry show us)

A

By morphology: Myeoloblasts have Auer Rods (also myeloblasts have more cytoplasm but thats beyond our scope)

By Immunophenotype:

  • Myeloid: CD13, 14, 15, 33, 117
  • Lymphoid: CD3, CD19, CD20
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13
Q

**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?

A

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
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14
Q

What age group typically gets ALL? What cells are present? Is there a preleukemia state like in AML?

A

children>adults

lymphoblasts

No pre-leukemia state ! AML has Myelodysplasia. but ALL doesn’t have that

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15
Q

What are the 2 classifications of ALL and what translocations are associated with each? Also how does the prognosis relate to the translocations?

A

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
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16
Q

What are 3 mature B cells markers? 3 immature markers?

A

B cell markers:

  • CD19(+)
  • CD22(+)
  • CD20(+/-)

Immature markers:

  • TDT(+)
  • CD34(+)
  • CD10(+) (sometimes)
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17
Q

What are the 5 things to consider when determining prognosis for B-ALL (B cell ALL)?

A

Age

Cytogenetics

WBC Count

CSF involvement

Marrow involvement following therapy

18
Q

What are 3 good prognostic indicators in B-ALL

A

age 2-10 y/o

hyperdiploidy (>50 chromosomes)

t(12;21)

19
Q

What are 6 BAD prognostic indicators in B-ALL?

A

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

20
Q

How do T-ALLs apear morphologically/ what do we find on flow cytometry?

How do they often present?

A

Meadiastinal masses in adolescents “thymic lymphomas”

May appear morphologically identical to B-ALL but flow cytometry shows: CD3(+), CD1a(+)

21
Q

What are the 4 options for treatment of all cancers?

(all, not acute lymphoid leukemia (ALL))

A

Chemotherapy

Targeted therapy: tyrosine kinase inhibitors

Cellular therapy: Stem cell transplant, CAR-T Cells

Immunotherapy: Inotuzumab, Blinatumimab

22
Q

How do we treat ALL?

A

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

23
Q

WHat are 3 hip new drugs that have drastically improved the survival for ALL?

A

Inotuzumab Ozogamicin

Blinatumomab (Bring the leukemia cells and your T cells together for better fighting)

Dasatinib-1st line for adults with philadelphia chromosome ALL

24
Q

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?

A

They are all the same! monoclonal! wooooooo!

Flow cytometry bc biopsy is invasive

25
Q

How do people describe the appearance of CLL cells?

A

Soccer ball chromatin

26
Q

What is the most likely immunophenotype of the lymphocytes in CLL? Is CLL indolent or aggressive?

A

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!

27
Q

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

A

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

28
Q

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?

A

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)

29
Q

CLL/SLL is a leukemia and a lymphoma. What is the significance of this?

A

It can involve the blood and bone marrow (leukemia) and lymph (lymphoma)

Involving the lymph means

  • tissue based
  • lymph nodes, spleen, MALT
30
Q

What does CLL/SLL look like as a lymphoma?

A

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

31
Q

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?

A

Small B cell leukemia/lymphoma that is….

CD5+: Mantle cell lymphoma or CLL/SLL

CD5-: Follicular lymphoma or marginal zone lymphoma

32
Q

What is the diagnosis if you have a small B cell leukemia/lymphoma that is

CD5+, CD23-, FMC7+

A

Mantle cell lymphoma

33
Q

What is the diagnosis if you have a small B cell leukemia/lymphoma that is

CD5+, CD23+, FMC7-

A

CLL/SLL

34
Q

What is the diagnosis if you have a small B cell leukemia/lymphoma that is

CD5-, CD10+

A

Follicular lymphoma

35
Q

What is the diagnosis if you have a small B cell leukemia/lymphoma that is

CD5-, CD10-

A

MALT lymphoma

36
Q

What are 3 good prognostic factors for CLL/SLL?

A

Low Rai stage

mutated IGHV gene

Deletion 13q

37
Q

What are 4 bad prognostic factors for CLL/SLL

A

High Rai stage

unmutated IGHV gene

CD38/ZAP-70 expression

Deletion 11q, 17p

38
Q

How do we determine which Rai stage someone is?

A

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

39
Q

How doe the prognosis change for CLL based on the Rai stage?

A

Stage 0- 150 months

stage I- 101 months

stage II- 71 months

stage III/IV- 9 months

40
Q

What are the lab parameters that indicate treatment of CLL? How about Clinical parameters?

A

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
41
Q

What do we worry that CLL may progress to?

A

B cell lymphoma, (Richter syndrome)