Hem 10 - Leukemia And Multiple Myeloma

Question 1

What are the symptoms of Acute leukemia?

Answer 1

Rapid onset and rapidly progressive. Over 50% myeloblasts (AML) or lymphoblasts (ALL) in the bone marrow. Numerous blast (immature) cells (more than 20% blasts). Often associated w/ pancytopenia (anemia, bleeding tendency, infection).

Question 2

What are the symptoms of Acute Lymphoblastic Leukemia?

Answer 2

Philadelphia chromosome may be seen (poor prognosis). Most common in children and young adults. Males and whites more affected. B cell types more common than T cell. 3 morphologic variants and 5 phenotypic variants. Bone pain is common. Most have the enzyme terminal deoxynucleotide transferasse (TdT). Very good prognosis in children (90% remission). PAS (+). Difficult to dx on blood smear (others can be dx w. this).

Question 3

What are the symptoms of Acute Myelogenous Leukemia?

Answer 3

Philadelphia chromosome rarely seen. Characteristic Auer rods. 8 different morphological classifications. Most ll are CD 13/33 (+). Usuallt nonspecific esterase (+) myeloid cells. Median age of onset is 65. PAS (-). Associated w/ numerous risk factors.

Question 4

Which type of leukemia is associated w/ Down syndrome?

Answer 4

[we ALL fall Down] Acute lymphoblastic leukemia is associated w/ Down syndrome.

Question 5

What are Auer rods?

Answer 5

Thin, reddish rods seen in the cytoplasm of the myeloblasts in AML. They are especially common in M3 variety: the Acute promyelocytic AML

Question 6

What are 3 risk factors for AML?

Answer 6

Radiation, benzene, or alkylating agents (such as in Hodgkin lymphoma treatment). Myeloproliferative disease, myelodysplastic syndrome, or aplastic anemia. Down syndrome, Fanconi anemia or Blood syndrome.

Question 7

What are the symptoms of Chronic Leukemia?

Answer 7

Insidious onset and gradual progression (months to years). Mature cells (rather than blasts; less than 5% blasts). Can be either myeloid (CML) or lymphoid (CLL). Associated w/ hepatosplenomegaly and lymphadenopathy. Prominent infiltration of bone marrow by leukemic cells and peripheral WBC counts may be high.

Question 8

What are traits seen in Chronic Lymphocytic Leukemia?

Answer 8

Most common adult leukemia seen in western country. Males and whites more affected. Seen in adults over 50. 95% have B cell markers (rather than T cell). 10% progress to ALL. Characteristic smudge cells. Autoimmune hemolytic anemia (Both cold and warm). Tends to be indolent.

Question 9

What are the traits seen in Chronic Myelogenous Leukemia?

Answer 9

May progress to AML (80%) or ALL (20%). Numerous basophils and PMNs are LAP (-). Seen in adults ages 25-60. Hyperplasia of all 3 cell lines (granulocytic, erythroid, and megakaryocytic) but granulocyte precursor predominate. Philadelphia chrom (t9;22) is always present. Fatigue, abdominal pain, splenomegaly, bleeding tendency.

Question 10

What are smudge cells?

Answer 10

Lymphocytes that instead of having a nice round nucleus, the nucleus is larger and irregular and the cytoplasm looks like it is smeared.

Question 11

What is Philadelphia chromosome?

Answer 11

Translocation 9;22. This creates mutation bcr-abl; it encodes constitutively activated tyrosine kinase. Always present in CML [Philadelphia CreaML cheese]. Sometimes present in ALL, rarely present in AML.

Question 12

Which drug specifically targets the Philadelphia chromosome and what is the mechanism?

Answer 12

Imatinib. It specifically inhibits bcr-abl tyrosine kinase.

Question 13

Which disease is associated w/ t(8;14)?

Answer 13

Burkitt lymphoma.

Question 14

Which disease is associated w/ t(15;17)?

Answer 14

M3 type of AML.

Question 15

Which disease is associated w/ t(9;22)?

Answer 15

Philadelphia chromosome in CML.

Question 16

Which disease is associated w/ t(8;21)?

Answer 16

AML.

Question 17

What is a Leukemoid reaction?

Answer 17

An elevated WBC as a reaction to a stressor, like an infection. Predominantly neutrophils. Left shift (5-10% immature band forms). Causes are infection, Down syndrome, congenital abnormalities (tetralogy of Fallot), Malignancy, Kawasaki disease, Heat stroke.

Question 18

What is Melodysplastic syndromes?

Answer 18

Dysplasia of the hematopoietic cells in the myeloid tissue. Causes Pelger-Huet anomaly on blood smear; neutrophils have nucleis w/ 2 lobes connected in the middle by a thin line. Most patients are asymptomatic and dx is made w/ bone marrow biopsy that shows dysplasia and disordered hematopoiesis.

Question 19

What is Myeloproliferative disorder?

Answer 19

Neoplastic transformation of a single myeloid precursor that causes monoclonal proliferation of mature myeloid cells. Three examples are polycythemia vera, essential thrombocytosis, and myelofibrosis. Associated w/ mutation of JAK2 (Turning it constitutively on): which encodes a protein called Janus Kinase 2 which is involved in hematopoietic growth factor signaling.

Question 20

What is Polycythemia vera?

Answer 20

A benign neoplasm of RBCs; increased red cell mass w/o elevated erythropoietin. Causes plethora, pruritus after hot bath or shower, splenomegaly, hiperviscosity of blood, headahce and erythromelalgia.

Question 21

What is Essential thrombocytosis?

Answer 21

The platelet equivalent of polycythemia vera; increased platelets with low thrombopoietin. They can have thrombosis. Or bleeding (because the platelets do not work correctly).

Question 22

What is Myelofibrosis?

Answer 22

Fibrosis and obliteration of marrow space. It causes tear-dropped shaped RBCs.

Question 23

What is Multiple myeloma?

Answer 23

Malignancy of plasma cells; a monoclonal plasma cell cancer. Plasma are fully differentiated B cells whose job is to produce antibodies. This diseases causes a huge production of antibodies, usually IgG, but sometimes IgA. Initially causes anemia (Crowding of bone marrow interferes w/ RBC production), renal insuff(Abs form casts in the urine and plug up the kidneys), back pain and hypercalcemia (they secrete cytokines called local osteolytic factors that stimulate osteoclast and inhibit osteoblasts). Shows up as monoclonal Ab spike (M spike) on serum protein electrophoresis (SPEP). Immunoglobin light chains in urine (Bence Jones proteins) detected on urine protein electrophoresis (UPEP). Leads to increased susceptibility to infection and amyloidosis. Causes punched-out lytic bone lesions (due to local osteolytic factors). Peripheral smear shows RBCs stacked up as coins (Rulou formation).

Question 24

What is Waldenstrom macroglobulinemia?

Answer 24

Causes monoclonal proliferation of IgM. Does not cause punched out bone lesions like in multiple myeloma. Associated w/ amyloidosis and hyperviscosity.

Question 25

What is a Plasmacytoma?

Answer 25

Solid tumor of plasma cells. 2 types: solitary plasmacytoma of bone and Extramedullary plasmacytoma (Predilection for head and neck). Do not cause lytic bone lesions.

Question 26

What is MGUS?

Answer 26

Monoclonal Gammopathy of Undetermined Significance. It is monoclonal proliferation of plasma cells that are producing lots of monoclonal immunoglobulins. It does not cause symptoms, but can progress to multiple myeloma.

Question 27

A patient w/ anemia, hypercalcemia, and bone pain undergoes a bone marrow biopsy, which reveals plasma cells. What is the diagnosis, and what may be found in urinalysis?

Answer 27

Multiple myeloma. No proteinuria on routine urinalysis, however there is monoclonal antibody spike on UPEP.

Question 28

What form of leukemia matches the following statement: Most common leukemia in children.

Answer 28

ALL.

Question 29

What form of leukemia matches the following statement: most common leukemia in adults in US?

Answer 29

CLL.

Question 30

What form of leukemia matches the following statement: characteristic Auer rods.

Answer 30

M3 AML.

Question 31

Myelodysplastic syndrome have a tendency to progress to…?

Answer 31

AML.

Question 32

Myeloproliferative disorders may progress to…?

Answer 32

AML.

Question 33

What form of leukemia matches the following statement: more than 20% blasts in marrow.

Answer 33

Acute leukemia.

Question 34

What form of leukemia matches the following statement: leukemia w/ more mature cells and less than 5% blasts.

Answer 34

Chronic leukemia.

Question 35

What form of leukemia matches the following statement: PAS (+) acute leukemia.

Answer 35

ALL.

Question 36

What form of leukemia matches the following statement: commonly presents w/ bone pain.

Answer 36

ALL.

Question 37

What form of leukemia matches the following statement: Numerous basophils, splenomegaly, and negative for leukocyte alkaline phosphate (LAP).

Answer 37

CML.

Question 38

What form of leukemia matches the following statement: Always positive for the Philadelphia chromosome (t 9;22).

Answer 38

CML.

Question 39

What form of leukemia matches the following statement: acute leukemia positive for perioxidase.

Answer 39

AML.

Question 40

What form of leukemia matches the following statement: solide sheets of lymphoblasts in marrow.

Answer 40

ALL.

Question 41

What form of leukemia matches the following statement: PAS (-) acute leukemia.

Answer 41

AML.

Question 42

What form of leukemia matches the following statement: always associated w/ bcr-abl gene.

Answer 42

CML.

Question 43

RFF: Smudge cells.

Answer 43

CLL.

Question 44

RFF: “punched out” lytic bone lesions.

Answer 44

Multiple myeloma.

Question 45

RFF: RBCs clumped together like a stack of coins.

Answer 45

Rouleaux formation (multiple myeloma).

Question 46

RFF: Monoclonal antibody spike.

Answer 46

Multiple myeloma, MGUS, Waldenstrom macroglobulinemia.

Question 47

RFF: Reddish-pink rods in the cytoplasm of leukemic blasts.

Answer 47

Auer rods in AML.