White Blood Cells and Lymph nodes, Part 2: Acute Leukemias

Question 1

what is this an example of ?

Answer 1

neoplastic proliferations of white cells

Question 2

what is this an example of?

Answer 2

neoplastic proliferation of white cells

Question 3

what are the different types of Neoplastic proliferations of white cells?

Answer 3

1. leukemia
2. lymphoma
3. plasma cell neoplasms

Question 4

what is leukemia?

Answer 4

• neoplastic disease because of uncontrolled proliferation and incomplete maturation of hematopoietic precursors in bone marrow; displacing the remaining “normal” cells
• cells then enter into circulation and may damage other reticuloendothelial organs

Question 5

neoplastic proliferation seen in leukemia is usually refered to as what?

presence of leukemia cells in peripheral blood leads to what?

Answer 5

“blast”

increase in total white cell counts

Question 6

what is this?

Answer 6

lymphoma

Question 7

what is this?

Answer 7

lymphoma

Question 8

what are lymphomas?

what is an example of the tissues where it arises?

what are the 2 main categories of lymphomas?

Answer 8

proliferations arising as discrete tissue masses

example: lymph nodes

1. Hodgkins lymphoma
2. non-hodgkins lymphoma

Question 9

what is this?

Answer 9

plasma cell neoplasm

Question 10

what are plasma cell neoplasms?

where do they arise?

Answer 10

plasma cell tumors or terminally diff. B cell

arise mostly from bone marrow,

Question 11

what are the Etiological and pathogenetic factors in white cell neoplasia?

what causes some of these?

Answer 11

1) Chromosomal translocation and other acquired mutations
2) Inherited genetic factors: Down syndrome, Bloom syndrome, Fanconi anemia, Ataxia telangiectasia
3) Viruses: HTLV-1, EBV, Kaposi sarcoma herpes virus/ human herpesvirus – 8 (KSHV/HHV-8)
4) Chronic immune stimulation: Helicobacter pylori association with gastric B- cell lymphoma (MALToma)
- gluten sensitivity enteropathy with intestinal T- cell lymphoma

Immune deficiency: Wiskott-Aldrich syndrome, HIV associated with B - cell lymphoma

5) Iatrogenic agents: radiation, chemotherapy, cigarette smoking

Question 12

what are the types of acute leukemias?

Answer 12

1) Acute Lymphoblastic Leukemia (ALL)
2) Acute Myelogenous Leukemia (AML)

Question 13

In what age group do we see ALL mostly?

In what age group do we see AML mostly?

what cells are seen in acute leukemias?

Answer 13

pediatric

40-60

“blasts”

Question 14

what are these?

Answer 14

blasts seen in acute leukemia

Question 15

what type of cell is ALL composed of?

the 85% of ALL cells are?

what cells does ALL affect in adolescents? What organ gets affected usually?

what are the risk factors for ALL?

What is the risk factor for T-cell ALL?

What is the risk factor for B-cell ALL?

what is the prognosis of B-cell ALL with t(9; 22) in adults?

what is the prognosis of B-cell ALL with t(9; 22) in children?

Answer 15

precursor B cells or T cells

pre-B cells

pre-T cells, thymus

chromosomal changes: especially Down syndrome (very likely to develop ALL)

NOTCH1 mutation

PAX5 mutation or translocation (12;21) involving ETV6/RUNX1, which promote maturation arrest

poor prognosis, good prognosis

Question 16

what is found in this peripheral blood smear?

Answer 16

leukemic blast cells of lymphoid origin

Question 17

what can we expect from these lab values from ALL?

WBC

Hb

Platelet

Peripheral smear

Bone Marrow

Answer 17

anemia, neutropenia and thrombocytopenia will be seen

WBC = elevated

Hb = decreased

Platelets = decreased

Peripheral blood smear = circulating leukemic blast cells

Bone Marrow = presence of leukemic blast cells of lymphoid origin (usually more than 20%)

Question 18

what is the most important organ to look at in a lab report for ALL?

how do you differentiate ALL from AML?

to make the distinction, what tool is used?

Answer 18

Bone Marrow

presence of lymphoblast will be seen and absence of Myeloblasts

use of histochemical staining for differentiation

Question 19

what is this?

Answer 19

lymphoblast

Question 20

what is this?

Answer 20

myeloblasts

Question 21

what is being used here? what is it determining?

what is it negative for?

Answer 21

myeloperoxidase positive test

determines AML

ALL

Question 22

what is being used here?

what is it determining?

what is it negative for?

Answer 22

sudan black positive

determines AML

ALL

Question 23

what is being used here?

what is it determining?

what is it negative for?

Answer 23

PAS

ALL

AML

Question 24

What will immunophenotyping reveal for ALL?

what is the only thing that wont be expressed by pre-B cell that will be by pre-T cell?

Answer 24

• terminal deoxynucleotidyltransferase (TdT)
• its expressed by both pre-B/T cell
• positive tdt indicates that the cells are blasts, as mature cells would be negative for tdt
• pre-B cell will show: CD10, CD19, PAX5
• pre-T cell will show: CD2, CD3, CD4, CD7 positive

CD10

Question 25

what can a biochemical test reveal about ALL? what other non-specific testing can reveal about ALL?

Answer 25

1. serum lactate dehydrogenase (LDH) = increased 2. serum uric acid = increased * chest X-ray: * thymic enlargement (with T- cell type ALL) * mediastinal lymph node (with T- cell type ALL)

Question 26

How important is CSF testing in ALL? What other area is tested in ALL, considered the same as CSF?

Answer 26

essential testes

Question 27

what is this?

Answer 27

lymphoblasts in a peripheral blood smear

Question 28

what are the clinical features of ALL? What is a characteristic symptom of T-ALL?

Answer 28

- anemia, neutropenia and thrombocytopenia\ - abrupt stormy onset, bone marrow depression, bone pain and tenderness, generalized lymphadenopathy, CNS manifestations T-ALL = anterior mediastinal lymphadenopathy

Question 29

What is the treatment for ALL?

Answer 29

traditionally, the four components of ALL treatment are induction, consolidation (daunorubicin and cytosine arabinoside (Ara-C)), maintenance, and central nervous system (CNS) prophylaxis

Question 30

what is Acute Myelogenous Leukemia? In what age group does it happen the most? what causes it?

Answer 30

tumor of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation leading to accumulation of immature myeloid blasts in bone marrow - adults 80% - radiation exposure, chronic benzene exposure, chemotherapeutic drugs, smoking, Down synd, Bloom synd, Fanconi anemia. AML following MDS.

Question 31

what is the pathophysiology of Acute Myeloid Leukemia?

Answer 31

* associated with acquired genetic alteration that inhibit terminal myeloid differentiation * marrow is then replaced by undifferentiated ‘blasts’ with features of early myeloid differentiation

Question 32

what are the most common chromosomal translocations leading to AML?

Answer 32

t(15;17) with M3, inv 16 with M4, t(8;21) with M2 AML following MDS

Question 33

what environmental factors may lead to AML?

Answer 33

rubber, paint, embalming fluid, ethylene oxide, petroleum products, ionizing radiation

Question 34

AML: M3 occurs on what population age? what can be seen characteristically in myeloid cells? what symptoms can be expected? what risk is there? what common feature can be seen? with what translocation is it associated?

Answer 34

young males mostly numerous Auer rods present bleeding tendencies DIC Bone Marrow failure t(15;17)

Question 35

what is this?

Answer 35

Predominantly promyelocytes Note: numerous granules also, numerous auer rods

Question 36

what is this?

Answer 36

M3 (Acute promyelocytic leukemia): majority of cells are heavily granulated leukemic promyelocytes

Question 37

what is the clinical sign of Acute Monocytic leukemia M5? for what test are people positive with AML M5? what is the prognosis for this?

Answer 37

bleeding tendency + CNS involvement and extramedullary features (include: cutaneous and gingival infiltration) positive for non-specific esterase (NSE) poor prognosis

Question 38

what can be expected in the lab values for Acute Myeloid Leukemia? Total white count Anemia? Thrombocytopenia? peripheral blood smear? Bone Marrow? Cytogenic studies?

Answer 38

Total white count = increased (could be decreased) Anemia = yes Thrombocytopenia = yes peripheral blood smear = presence of atypical myeloid cells and circulating "blasts" Bone Marrow = more than 20% blasts

Question 39

what can be noted in this peripheral blood smear?

Answer 39

Auer rods

Question 40

what are the clinical features of Acute Myeloid Leukemia?

Answer 40

Clinical Features: * fever, splenomegaly, hepatomegaly, lymphadenopathy * sternal tenderness, evidence of infection, hemorrhage * easy bruising, petechiae, epistaxis, gingival bleeding, conjunctival hemorrhages, and prolonged bleeding from skin injuries… * reflect thrombocytopenia and are frequent early manifestations of the disease

Question 41

what are the clinical signs for Acute Myeloid Leukemia for M3? what are the clinical signs for Acute Myeloid Leukemia for M5? what are the clinical signs for Acute Myeloid Leukemia for M7?

Answer 41

gastrointestinal, intrapulmonary or intracranial hemorrhages, DIC gingival infiltration, meningeal involvement increased association with Down syndrome

Question 42

what is a Myeloid (Granylocytic) Sarcoma? how does it occur?

Answer 42

Myeloid sarcoma (also known as granulocytic sarcoma, chloroma, myeloblastoma, monocytoma) is a tumor composed of myeloblasts, monoblasts, or megakaryocytes occur as extramedullary masses (including the skin; orbit; paranasal sinuses; chest wall; breast; heart; gastrointestinal, respiratory, or genitourinary tract; central or peripheral nervous system; and spleen)

Question 43

what is the prognosis of AML? what is the only means to induce a sustained remission in patients with AML who do not enter remission with cytotoxic drug therapy or who relapse after a first remission?

Answer 43

15-30% remain free of disease for 5 years using allogeneic stem cell transplantation