Heme 03: Lymphoid Leukemia Applications

Front 1

Case 1: 29 yo male presents complaining of SOB while jogging and progressive fatigue for 3 weeks. He usually runs several miles a day. He has felt well aside from this, has not had fever, weight change, loss of appetite, muscle aches, sweats, bruising, or bleeding.

WBC: 11.3 / µL w/ abnormal WBCs on peripheral blood smear.

Which of the following pictures reveals cells that are abnormal in the blood?

Back 1

B - blasts

Front 2

Case 1: 29 yo male presents complaining of SOB while jogging and progressive fatigue for 3 weeks. He usually runs several miles a day. He has felt well aside from this, has not had fever, weight change, loss of appetite, muscle aches, sweats, bruising, or bleeding.

WBC: 11.3 / µL w/ abnormal WBCs on peripheral blood smear.

Differential shows 60% blasts. What is the correct statement above?

Back 2

They are immature cells

Front 3

Case 1: 29 yo male presents complaining of SOB while jogging and progressive fatigue for 3 weeks. He usually runs several miles a day. He has felt well aside from this, has not had fever, weight change, loss of appetite, muscle aches, sweats, bruising, or bleeding.

WBC: 11.3 / µL w/ abnormal WBCs on peripheral blood smear.

Differential shows 60% blasts. What test can you do to further characterize these cells?

Back 3

Flow Cytometry - figure out definitively what kind of cells these are

Front 4

Case 1: 29 yo male presents complaining of SOB while jogging and progressive fatigue for 3 weeks. He usually runs several miles a day. He has felt well aside from this, has not had fever, weight change, loss of appetite, muscle aches, sweats, bruising, or bleeding.

WBC: 11.3 / µL w/ abnormal WBCs on peripheral blood smear.

Differential shows 60% blasts. Flow Cytometry shows they are positive for CD10, CD19, CD34 and negative for CD3 and CD20. Similar cells (as those found in PB) may be observed in what other tissue sites?

Back 4

- Cerebrospinal Fluid
- Lymph nodes
- Bone marrow
- Splenic sinusoids

Front 5

Case 1: 29 yo male presents complaining of SOB while jogging and progressive fatigue for 3 weeks. He usually runs several miles a day. He has felt well aside from this, has not had fever, weight change, loss of appetite, muscle aches, sweats, bruising, or bleeding.

WBC: 11.3 / µL w/ abnormal WBCs on peripheral blood smear.

Differential shows 60% blasts positive for CD10, CD19, and CD34, but negative for CD3 and CD20.

What are the expected findings in the bone marrow?

Back 5

- Cells with cytogenetic abnormalities
- Hypercellularity

Front 6

Case 1: 29 yo male presents complaining of SOB while jogging and progressive fatigue for 3 weeks. He usually runs several miles a day. He has felt well aside from this, has not had fever, weight change, loss of appetite, muscle aches, sweats, bruising, or bleeding.

WBC: 11.3 / µL w/ abnormal WBCs on peripheral blood smear.

Differential shows 60% blasts positive for CD10, CD19, and CD34, but negative for CD3 and CD20.

Results of cytogenetic analysis of diagnostic BM shown above. No translocations identified. What do these cytogenetic results imply?

Back 6

This is a favorable cytogenetic finding for the diagnosis of B-ALL, the following are the favorable prognostic features:
- Hyperploidy (extra chromosomes)
- Trisomy of chromosomes 4 and 7 (10 is also favorable if present)

Front 7

Case 1: If this patient were an adolescent male presenting with a large mediastinal mass, what would be an expected in the mediastinal biopsy?

Back 7

CD3(+) tumor cells (because it is a T cell neoplasm)

Front 8

What diagnosis and kind of symptoms would you predict for this patient?

Back 8

CLL: soccer ball chromatin or ginger snap chromatin
- Often asymptomatic
- Indolent, non-symptom presentation
- Diagnose as incidental finding on routine CBC
- May have extensive adenopathy and organomegaly

Front 9

What is the expected patient profile for this finding?

Back 9

Older patient (more common in CLL)

Front 10

Is this expected to be immunophenotypically normal or abnormal? Monoclonal or polyclonal?

Back 10

- Immunophenotypically abnormal
- Monoclonal B cells (they all look the same so probably from the same precursor)

Front 11

What diagnosis would you predict for this patient?

Back 11

Infectious Mononucleosis

Front 12

What is the expected patient profile for this finding?

Back 12

Young teenager (more common for Infectious Mononucleosis)

Front 13

Is this expected to be immunophenotypically normal or abnormal? Monoclonal or polyclonal?

Back 13

- Immunophenotypically normal
- Polyclonal B cells (they all look different so they are reactive lymphocytes)

Front 14

Case 3: 65 yo female presents with fatigue for 6 months. Discomfort in LUQ recently and decrease in appetite. Several, firm, mobile, lymph nodes 1-1.5 cm in posterior triangles on both sides of neck and tip of spleen is palpable.

WBC count: 60,000/µL w/ 90% lymphocytes, 8% neutrophils, 2% eosinophils. Hemoglobin 9g/dL and platelets 50,000/µL.

Which is true?

Back 14

C - peripheral blood lymphocytes have the same immunophenotype as those in the lymph nodes and spleen

Reactive processes don't get above 10,000/µL, so you know this is neoplastic, therefore whatever is in lymph nodes and spleen should be the same as in blood

Front 15

Case 3: 65 yo female presents with fatigue for 6 months. Discomfort in LUQ recently and decrease in appetite. Several, firm, mobile, lymph nodes 1-1.5 cm in posterior triangles on both sides of neck and tip of spleen is palpable.

WBC count: 60,000/µL w/ 90% lymphocytes, 8% neutrophils, 2% eosinophils. Hemoglobin 9g/dL and platelets 50,000/µL.

What is the absolute lymphocyte count in this case?

Back 15

54,000 / µL

Front 16

Case 3: 65 yo female presents with fatigue for 6 months. Discomfort in LUQ recently and decrease in appetite. Several, firm, mobile, lymph nodes 1-1.5 cm in posterior triangles on both sides of neck and tip of spleen is palpable.

WBC count: 60,000/µL w/ 90% lymphocytes, 8% neutrophils, 2% eosinophils. Hemoglobin 9g/dL and platelets 50,000/µL.

Based on the peripheral smear provided, what is the most likely immunophenotype of the lymphocytes?

Back 16

CD5+, CD20+, CD23+ cells expressing kappa (or lambda, just can only be one) light chain only (immunophenotype for CLL)

Front 17

Case 3: 65 yo female presents with fatigue for 6 months. Discomfort in LUQ recently and decrease in appetite. Several, firm, mobile, lymph nodes 1-1.5 cm in posterior triangles on both sides of neck and tip of spleen is palpable.

WBC count: 60,000/µL w/ 90% lymphocytes, 8% neutrophils, 2% eosinophils. Hemoglobin 9g/dL and platelets 50,000/µL.

What is the most likely reason the patient is cytopenic (anemia and thrombocytopenia)?

Back 17

Bone marrow replaced w/ neoplastic cells

Front 18

Case 3: 65 yo female presents with fatigue for 6 months. Discomfort in LUQ recently and decrease in appetite. Several, firm, mobile, lymph nodes 1-1.5 cm in posterior triangles on both sides of neck and tip of spleen is palpable.

WBC count: 60,000/µL w/ 90% lymphocytes, 8% neutrophils, 2% eosinophils. Hemoglobin 9g/dL and platelets 50,000/µL.

When the diagnosis (CLL) is established, the patient opts for no treatment. What kind of clinical course does CLL have?

Back 18

Indolent clinical course

Front 19

Case 3: 65 yo female presents with fatigue for 6 months. Discomfort in LUQ recently and decrease in appetite. Several, firm, mobile, lymph nodes 1-1.5 cm in posterior triangles on both sides of neck and tip of spleen is palpable.

WBC count: 60,000/µL w/ 90% lymphocytes, 8% neutrophils, 2% eosinophils. Hemoglobin 9g/dL and platelets 50,000/µL.

Three months later she presents w/ night sweats, fever, and 20 lb weight loss and a lump in her neck. Biopsy reveals aggressive lymphoma.

What poor prognostic indicators of CLL might have been present at diagnosis?

Back 19

- Presence of deletions of 11q and 17p
- Lack of somatic hypermutation
- Expression of ZAP-70 (protein that augments signals produced by Ig receptor)

Front 20

What defines an absolute lymphocytosis?

Back 20

≥ 4000 lymphocytes / µL

Front 21

What are the benign causes of lymphocytosis?

Back 21

* Infectious mononucleosis (common)
* IM-like syndromes, eg, CMV, adenovirus, acute HIV, toxoplasmosis (common)
* Transient stress lymphocytosis (common)

- Other viruses (hepatitis, chickenpox)
- Drugs
- Whooping cough
- Persistent polyclonal B-cell lymphocytosis

Front 22

What are the neoplastic causes of lymphocytosis?

Back 22

- Leukemic lymphoma
- Sézary syndrome
- Hairy cell leukemia
- T/NK cell large granular lymphocytic leukemia

- Chronic Lymphocytic Leukemia
- Adult T-cell Leukemia

Front 23

What are the immunophenotypical signs of AML?

Back 23

- CD13
- CD14
- CD15
- CD33
- CD117

Front 24

What are the immunophenotypical signs of ALL?

Back 24

- CD3
- CD19
- CD20

Front 25

How do AML and ALL compare in terms of common age of onset?

Back 25

- AML: ADULTS > children
- ALL: CHILDREN > adults

Front 26

How do AML and ALL compare in terms of morphology?

Back 26

- AML: myeloblasts ± Auer rods (may have granulocytic, erythroid, megakaryocytic, or monocytic differentiation)

- ALL: lymphoblasts

Front 27

What is the pre-leukemic state for AML vs ALL?

Back 27

- AML: myelodysplasia syndrome

- ALL: no pre-leukemic state

Front 28

How do you classify AML types?

Back 28

- AML w/ recurrent cytogenetic abnormalities
- AML w/ myelodysplasia associated changes
- AML / MDS, therapy-related
- AML, not otherwise specified

Front 29

How do you classify ALL types?

Back 29

85% B-cell ALLs
- t(12;21) most common in kids
- t(9;22) poor prognosis

15% T-cell ALLs
- Adolescent males w/ mediastinal masses
- Worse prognosis

Front 30

What are the good prognostic factors for B-ALL?

Back 30

- 1-10 years
- Hyperdiploidy (>50 chromosomes)
- t(12;21)

Front 31

What are the poor prognostic factors for B-ALL?

Back 31

- < 1 yo, >10 yo
- t(9;22)
- Hypodiploidy (<45 chromosomes)
- Elevated WBC count (>100,000/µL)
- CSF involvement
- Marrow involvement at day 15

Front 32

What is the classic presentation of T-ALL?

Back 32

Mediastinal mass in adolescents - thymic lymphoma

Front 33

How does T-ALL compare to B-ALL morphologically?

Back 33

- May appear identical morphologically
- T-ALL flow cytometry: CD3+, CD1a+

Front 34

What are the types of Small B cell Leukemia / Lymphomas?

Back 34

- Mantle Cell Lymphoma
- CLL/SLL
- Follicular Lymphoma
- MALT Lymphoma

Front 35

How do you distinguish Mantle Cell Lymphoma from the other small B cell leukemia / lymphomas?

Back 35

CD5+

CD23- / FMC7+

Front 36

How do you distinguish CLL/SLL from the other small B cell leukemia / lymphomas?

Back 36

CD5+

CD23+ / FMC7-

Front 37

How do you distinguish Follicular Lymphoma from the other small B cell leukemia / lymphomas?

Back 37

CD5-

CD10+

Front 38

How do you distinguish MALT Lymphoma / Marginal Zone Lymphoma from the other small B cell leukemia / lymphomas?

Back 38

CD5-

CD10-

Front 39

Which of the small B cell leukemia / lymphomas are CD5+? How do you distinguish them?

Back 39

- Mantle Cell Lymphoma: CD23- / FMC7+
- CLL/SLL: CD23+/FMC7-

Front 40

Which of the small B cell leukemia / lymphomas are CD5-? How do you distinguish them?

Back 40

- Follicular Lymphoma: CD10+
- MALT Lymphoma / Marginal Zone Lymphoma: CD10-

Front 41

What are the good prognostic indicators in CLL/SLL?

Back 41

- Low Rai stage
- Mutated IGHV gene
- Deletion 13q

Front 42

What are the poor prognostic indicators in CLL/SLL?

Back 42

- High Rai stage
- Unmutated IGHV gene
- CD38 / ZAP-70 expression
- Deletion 11q, 17p

Front 43

What is the staging system for CLL/SLL? Implications?

Back 43

Rai Staging System
- 0: lymphocytosis
- I: + adenopathy
- II: + organomegaly
- III: + anemia
- IV: + thrombocytopenia

The lower the stage the better the prognosis

Front 44

What neoplasms present with atypical lymphocytes ± lymphocytosis?

Back 44

- CLL/SLL
- Leukemic lymphoma (follicular, mantle, etc)
- Hairy cell leukemia
- Adult T cell leukemia/lymphoma
- Sézary syndrome

Front 45

What is the characteristic presentation of Hairy Cell Leukemia?

Back 45

Middle aged (40-60yo) male

Front 46

What are the exam findings of Hairy Cell Leukemia?

Back 46

*Indolent
- Splenomegaly (d/t red pulp infiltration)
- Pancytopenia
- Lymphocytes w/ "hairy projections" ± lymphocytosis
- TRAP+ cells
- Fibrosis in marrow ("dry tap")

Front 47

What causes splenomegaly in Hairy Cell Leukemia?

Back 47

Red Pulp infiltration

Front 48

What are the morphological characteristics of Hairy Cell Leukemia?

Back 48

Lymphocytes have 'hairy projections'

Front 49

What are the features of Hairy Cell Leukemia on flow cytometry?

Back 49

Bright CD11c and CD22 expression

Front 50

What cells are proliferating in Sézary Syndrome?

Back 50

CD4+ T cells

Front 51

What is the triad of symptoms in Sézary Syndrome?

Back 51

- Erythroderma
- Generalized lympadenopathy
- Circulating Sézary cells

Front 52

What are "Sézary cells"?

Back 52

CD4+ T cells that have "cerebriform" nuclei (look like brains)

Front 53

What is Sézary Syndrome related to? Symptoms?

Back 53

Mycosis Fungoides: patches, plaques

Front 54

What can Sézary Syndrome / Mycosis Fungoides transform into?

Back 54

Aggressive T cell tumor

Front 55

What kind of cells are affected by Adult T-cell Leukemia / Lymphoma?

Back 55

CD4+ T-cells

Front 56

What infection is Adult T-cell Leukemia / Lymphoma associated with?

Back 56

HTLV-1 infection (most w/ infection do NOT develop ATLL)

Front 57

Where is Adult T-cell Leukemia / Lymphoma more common?

Back 57

Japan, Caribbean, and Africa

Front 58

What is the appearance and symptoms of Adult T-cell Leukemia / Lymphoma?

Back 58

- "Flower cell" w/ lymphocytosis
- Hypercalcemia
- Aggressive