Hem & Onc - Pathology (Leukemias & Myelodysplastic syndromes )

Question 1

What phrase characterizes leukemia?

Answer 1

Unregulated growth of leukocytes in bone marrow

Question 2

What general effects can leukemia have on hematologic components?

Answer 2

Unregulated growth of leukocytes in bone marrow –> (1) Increased or decreased number of circulating leukocytes in blood & marrow failure –> (2) Anemia (decreased RBCs) (3) Infections (decreased mature WBCs) (4) Hemorrhage (decreased platelets)

Question 3

Where can leukemic cell infiltrates be found?

Answer 3

Leukemia cell infiltrates in liver, spleen, and lymph nodes are possible

Question 4

What are the 3 major kinds of lymphoid neoplasms in leukemia?

Answer 4

(1) Acute lymphoblastic leukemia/lymphoma (ALL) (2) Small lymphocytic lymphoma (SLL) / Chronic lymphocytic leukemia (CLL) (3) Hairy cell leukemia

Question 5

In what age group do you typically see Acute lymphoblastic leukemia/lymphoma (ALL)?

Answer 5

Age: < 15 years

Question 6

How can T-cell ALL present, and why?

Answer 6

Mediastinal mass (leukemic infiltration of thymus)

Question 7

What effect does ALL have on peripheral blood and bone marrow?

Answer 7

Very significant increase (3 arrows up) of lymphoblasts (blood smear shows large nucleus - about 2x size of RBCs instead of the normal standard of being same size)

Question 8

What are significant markers for ALL?

Answer 8

TdT+ (marker of pre-T cand pre-B cells); CD10+ (pre-B cells only).

Question 9

What is the ALL response to therapy like? What leads to a better prognosis?

Answer 9

Most responsive to therapy; t(12;21) => better prognosis

Question 10

Where might ALL spread?

Answer 10

CNS & testes

Question 11

In what age group do you typically see SLL/CLL?

Answer 11

Age: > 60 years

Question 12

How does SLL/CLL often present? What is its progression? What is found on peripheral blood smear?

Answer 12

Often asymptomatic; Progresses slowly; Smudge cells in peripheral smear

Question 13

With what hematologic condition is SLL/CLL associated?

Answer 13

Autoimmune hemolytic anemia

Question 14

What is the difference between SLL and CLL, if any?

Answer 14

SLL same as CLL, except CLL has increased peripheral blood lymphocytosis or bone marrow involvement

Question 15

What age group does hairy cell leukemia typically affected? How is it characterized/defined?

Answer 15

Age: Adults; Mature B-cell tumor in the elderly

Question 16

How does hairy cell leukemia appear on blood smear?

Answer 16

Cells have filamentous, hair-like projections

Question 17

What stain was used for hairy cell leukemia? What change has been made related to this diagnosis technique?

Answer 17

Stains TRAP (tartate-resistant acid phosphatase) positive; TRAP stain largely replaced with flow cytometry.

Question 18

How is hairy cell leukemia treated, and what kind of compound is this?

Answer 18

Cladribine (2-CDA), an adenosine analog (resistant to adenosine deaminase degradation)

Question 19

With what condition is Acute lymphoblastic leukemia/lymphoma (ALL) associated?

Answer 19

Associated with Down syndrome.

Question 20

What type of cell neoplasm is associated with SLL/CLL? What are its cell markers?

Answer 20

CD20+, CD5+ B-cell neoplasm

Question 21

What is found on blood smear in SLL/CLL?

Answer 21

Smudge cells in peripheral blood smear

Question 22

What effect does Hairy cell leukemia have on the marrow, and how does this manifest clinically?

Answer 22

Causes marrow fibrosis –> dry tap on aspiration.

Question 23

What are 2 types of myeloid neoplasms?

Answer 23

(1) Acute myelogenous leukemia (AML) (2) Chronic myelogenous leukemia (CML)

Question 24

What is the age of median onset of Acute myelogenous leukemia (AML)?

Answer 24

Age: median onset 65 years; Adults

Question 25

What histological/lab finding is associated with AML? Describe it and give the context in which it is mostly found.

Answer 25

Auer rods = peroxidase + cytoplasmic inclusions seen mostly in M3 AML

Question 26

What is the significant smear finding found in AML?

Answer 26

Markedly increased circulating myeoblasts on peripheral smear

Question 27

What are 4 risk factors for AML?

Answer 27

Risk factors: (1) prior exposure to alkylating chemotherapy (2) radiation (3) myeloproliferative disorders (4) Down syndrome

Question 28

What is the chromosomal translocation associated with a particular subtype of AML? What is that specific type? To what does it respond, and what effect does this have?

Answer 28

t(15;17) –> M3 AML subtype responds to all-trans retinoic acid (vitamin A), inducing differentiation of myeloblasts

Question 29

What is a common presentation in M3 AML?

Answer 29

DIC is a common presentation in M3 AML (Think: Auer rod release may induce it, but mechanism not understood)

Question 30

What is another name for a t(9;22) chromosomal translocation? With what disorder is it associated? What is its phenotypic change?

Answer 30

t (9;22) (Philadelphia chromosome); CML (bcr-abl hybrid); Think: “Philadelphia CreaML cheese”

Question 31

With what disorder is the t(8;14) chromosomal translocation associated? What is its phenotypic change?

Answer 31

Burkitt lymphoma (c-myc activation)

Question 32

With what disorder is the t(11;14) chromosomal translocation associated? What is its phenotypic change?

Answer 32

Mantle cell lymphoma (cyclin D1 activation)

Question 33

With what disorder is the t(14;18) chromosomal translocation associated? What is its phenotypic change?

Answer 33

Follicular lymphomas (bcl-2 activation)

Question 34

With what disorder is the t(15;17) chromosomal translocation associated? To what therapy is it responsive?

Answer 34

M3 type of AML (responsive to all-trans retinoic acid)

Question 35

What are the peak incidence and median diagnosis ages for Chronic myelogenous leukemous (CML)?

Answer 35

Age: peak incidence 45-85 years, median age at diagnosis 64 years.

Question 36

What characteristic defines CML?

Answer 36

Defined by the Philadelphia chromosome (t[9;22], bcr-abl)

Question 37

What kind of proliferation occurs in CML?

Answer 37

Myeloid stem cell proliferation

Question 38

How does CML present in terms of cell findings?

Answer 38

Presents with increased neutrophils, metamyelocytes, basophils

Question 39

What physical exam finding is associated with CML?

Answer 39

Splenomegaly

Question 40

What is the relation between AML or ALL and CML?

Answer 40

CML may accelerate and transform to AML or ALL (“blast crisis”)

Question 41

How is CML distinguished from leukemoid reaction?

Answer 41

Very low leukocyte alkaline phosphatase (LAP) as a result of low activity in mature granulocytes (vs. leukemoid reaction, in which LAP is high)

Question 42

To what therapy does CML respond? What is the mechanism of this therapy?

Answer 42

Responds to imatinib (a small-molecule inhibitor of the bcr-abl tyrosine kinase)

Question 43

What kind of disorders are myelodysplastic syndromes, and what pathophysiological effects do they have?

Answer 43

Stem cell disorders involving ineffective hematopoiesis –> defects in cell maturation of all non-lymphoid lineages

Question 44

What are 2 causes of myelodysplastic syndromes?

Answer 44

Causes by de novo mutations or environmental exposure (e.g., radiation, benzene, chemotherapy).

Question 45

What are 3 examples of environmental exposures that may cause myelodysplastic syndrome?

Answer 45

Environmental exposures (e.g., radiation, benzene, chemotherapy)

Question 46

What risk results from myelodysplastic syndrome?

Answer 46

Risk of transformation to AML

Question 47

What is Pseudo-Pelger-Huet anomaly, and when is it typically seen? With what disorder is it associated?

Answer 47

Pseudo-Pelger-Huet anomaly - neutrophils with bilobed nuclei (two nuclear masses connected with a thin filament of chromatin) typically seen after chemotherapy; Myelodysplastic syndromes