Flashcards in Hem & Onc - Pathology (Leukemias & Myelodysplastic syndromes ) Deck (47):
What phrase characterizes leukemia?
Unregulated growth of leukocytes in bone marrow
What general effects can leukemia have on hematologic components?
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)
Where can leukemic cell infiltrates be found?
Leukemia cell infiltrates in liver, spleen, and lymph nodes are possible
What are the 3 major kinds of lymphoid neoplasms in leukemia?
(1) Acute lymphoblastic leukemia/lymphoma (ALL) (2) Small lymphocytic lymphoma (SLL) / Chronic lymphocytic leukemia (CLL) (3) Hairy cell leukemia
In what age group do you typically see Acute lymphoblastic leukemia/lymphoma (ALL)?
Age: < 15 years
How can T-cell ALL present, and why?
Mediastinal mass (leukemic infiltration of thymus)
What effect does ALL have on peripheral blood and bone marrow?
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)
What are significant markers for ALL?
TdT+ (marker of pre-T cand pre-B cells); CD10+ (pre-B cells only).
What is the ALL response to therapy like? What leads to a better prognosis?
Most responsive to therapy; t(12;21) => better prognosis
Where might ALL spread?
CNS & testes
In what age group do you typically see SLL/CLL?
Age: > 60 years
How does SLL/CLL often present? What is its progression? What is found on peripheral blood smear?
Often asymptomatic; Progresses slowly; Smudge cells in peripheral smear
With what hematologic condition is SLL/CLL associated?
Autoimmune hemolytic anemia
What is the difference between SLL and CLL, if any?
SLL same as CLL, except CLL has increased peripheral blood lymphocytosis or bone marrow involvement
What age group does hairy cell leukemia typically affected? How is it characterized/defined?
Age: Adults; Mature B-cell tumor in the elderly
How does hairy cell leukemia appear on blood smear?
Cells have filamentous, hair-like projections
What stain was used for hairy cell leukemia? What change has been made related to this diagnosis technique?
Stains TRAP (tartate-resistant acid phosphatase) positive; TRAP stain largely replaced with flow cytometry.
How is hairy cell leukemia treated, and what kind of compound is this?
Cladribine (2-CDA), an adenosine analog (resistant to adenosine deaminase degradation)
With what condition is Acute lymphoblastic leukemia/lymphoma (ALL) associated?
Associated with Down syndrome.
What type of cell neoplasm is associated with SLL/CLL? What are its cell markers?
CD20+, CD5+ B-cell neoplasm
What is found on blood smear in SLL/CLL?
Smudge cells in peripheral blood smear
What effect does Hairy cell leukemia have on the marrow, and how does this manifest clinically?
Causes marrow fibrosis --> dry tap on aspiration.
What are 2 types of myeloid neoplasms?
(1) Acute myelogenous leukemia (AML) (2) Chronic myelogenous leukemia (CML)
What is the age of median onset of Acute myelogenous leukemia (AML)?
Age: median onset 65 years; Adults
What histological/lab finding is associated with AML? Describe it and give the context in which it is mostly found.
Auer rods = peroxidase + cytoplasmic inclusions seen mostly in M3 AML
What is the significant smear finding found in AML?
Markedly increased circulating myeoblasts on peripheral smear
What are 4 risk factors for AML?
Risk factors: (1) prior exposure to alkylating chemotherapy (2) radiation (3) myeloproliferative disorders (4) Down syndrome
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?
t(15;17) --> M3 AML subtype responds to all-trans retinoic acid (vitamin A), inducing differentiation of myeloblasts
What is a common presentation in M3 AML?
DIC is a common presentation in M3 AML (Think: Auer rod release may induce it, but mechanism not understood)
What is another name for a t(9;22) chromosomal translocation? With what disorder is it associated? What is its phenotypic change?
t (9;22) (Philadelphia chromosome); CML (bcr-abl hybrid); Think: "Philadelphia CreaML cheese"
With what disorder is the t(8;14) chromosomal translocation associated? What is its phenotypic change?
Burkitt lymphoma (c-myc activation)
With what disorder is the t(11;14) chromosomal translocation associated? What is its phenotypic change?
Mantle cell lymphoma (cyclin D1 activation)
With what disorder is the t(14;18) chromosomal translocation associated? What is its phenotypic change?
Follicular lymphomas (bcl-2 activation)
With what disorder is the t(15;17) chromosomal translocation associated? To what therapy is it responsive?
M3 type of AML (responsive to all-trans retinoic acid)
What are the peak incidence and median diagnosis ages for Chronic myelogenous leukemous (CML)?
Age: peak incidence 45-85 years, median age at diagnosis 64 years.
What characteristic defines CML?
Defined by the Philadelphia chromosome (t[9;22], bcr-abl)
What kind of proliferation occurs in CML?
Myeloid stem cell proliferation
How does CML present in terms of cell findings?
Presents with increased neutrophils, metamyelocytes, basophils
What physical exam finding is associated with CML?
What is the relation between AML or ALL and CML?
CML may accelerate and transform to AML or ALL ("blast crisis")
How is CML distinguished from leukemoid reaction?
Very low leukocyte alkaline phosphatase (LAP) as a result of low activity in mature granulocytes (vs. leukemoid reaction, in which LAP is high)
To what therapy does CML respond? What is the mechanism of this therapy?
Responds to imatinib (a small-molecule inhibitor of the bcr-abl tyrosine kinase)
What kind of disorders are myelodysplastic syndromes, and what pathophysiological effects do they have?
Stem cell disorders involving ineffective hematopoiesis --> defects in cell maturation of all non-lymphoid lineages
What are 2 causes of myelodysplastic syndromes?
Causes by de novo mutations or environmental exposure (e.g., radiation, benzene, chemotherapy).
What are 3 examples of environmental exposures that may cause myelodysplastic syndrome?
Environmental exposures (e.g., radiation, benzene, chemotherapy)
What risk results from myelodysplastic syndrome?
Risk of transformation to AML