Pathology of White Blood Cells, Lymph Nodes, Spleen, and Thymus (Part 4 of 4)

Question 1

What is acute myeloid leukemia?

Answer 1

mutations to hematopoietic stem cells or progenitor cells that allow for the development of a “leukemic stem cell”

Question 2

What is the malignancy of in AML?

Answer 2

myeloid progenitors

Question 3

what is the diagnostic criteria for AML?

Answer 3

> 20% BLASTS in bone marrow

Question 4

How does AML present? (5)

Answer 4

fever, fatigue, bleeding/bruising, and pancytopenia

Question 5

how does the peripheral blood look in AML patients?

Answer 5

normal/ no blasts in peripheral smear- you have to go to the bone marrow

Question 6

what is the bone marrow full of in AML patients?

Answer 6

myeloblasts

Question 7

What are the 4 ways AML can be classified?

Answer 7

AML with genetic aberrations, AML with MDS-like features, AML-therapy related, and AML not otherwise specified

Question 8

What are the two different genetic aberrations associated with AML?

Answer 8

t(8;21) and t(15;17)

Question 9

what does AML with t(8;21) usually show? and what are the characteristics of AML with t(8;21)

Answer 9

neutrophilic maturation- you can actually see the granules in the blasts; often younger patients and they have a good prognosis

Question 10

What is AML with a t(8;21) genetic aberration sometimes called?

Answer 10

CBF leukemia

Question 11

What occurs in the t(8;21) genetic aberration?

Answer 11

the RUNX-1-RUNX1T1 fusion product disrupts the core binding factor-mediated hematopoietic differentiation and maturation

Question 12

what is AML with t(15;17) genetic aberration often referred to as?

Answer 12

acute promyelocytic leukemia

Question 13

What is characteristic of AML with t(15;17)?

Answer 13

Auer rods are seen in the cytoplasm of the promyelocyte

Question 14

What is the function of normal RAR?

Answer 14

it helps drive neutrophilic differentiation forward

Question 15

what happens to the RAR in AML patients with t(15;17)?

Answer 15

the retinoic acid that binds and drives this forward is no longer liked by the receptor, so the fusion product creates a distaste for RA

Question 16

What is the treatment for AML t(15;17)?

Answer 16

all trans RA

Question 17

what are individuals with t(15;17) AML at risk for?

Answer 17

DIC

Question 18

why are individuals with AML t(15;17) at risk for DIC?

Answer 18

the leukemic cells express tissue factor, which activates factor X; high levels of annexin II receptors on plasma cells convert plasminogen into plasmin

Question 19

What are unusual presentations of AML?

Answer 19

acute monocytic leukemia (morphologic (M5) and extranodal involvement is common (including gingival and leukemia cutis)) and soft tissue mass formation

Question 20

What is the soft tissue mass formation named as in a patient with AML?

Answer 20

granulocytic sarcoma/myeloid sarcoma/ “chloroma”

Question 21

what stain is used to diagnose a granulocytic sarcoma/myeloid sarcoma/ “chloroma”?

Answer 21

myeloperoxidase stain

Question 22

What is myelodysplastic syndrome?

Answer 22

a clonal disorder with morphologic manifestations that can range through many cell lineages

Question 23

what is MDS considered to be a precursor to?

Answer 23

AML

Question 24

transformation of MDS into AML is most likely when?

Answer 24

if MDS is due to prior cytotoxic therapy/radiation (t-MDS)

Question 25

how do patients with myelodysplastic syndrome present?

Answer 25

cytopenias (most commonly anemia)

Question 26

What is classification of MDS based on?

Answer 26

dysmorphic features in one or more lineages, chromosomal analysis, and if blast count is increased (but not quite to the point of AML)

Question 27

What percentage of blasts gives you MDS RAEB-1?

Answer 27

5-9%

Question 28

what percentage of blasts gives you MDS RAEB-2?

Answer 28

10-19%

Question 29

When looking at dysmorphic features in MDS patients, what are 4 potential morphologies?

Answer 29

dyserythropoiesis, ring sideroblasts, pseudo pelger-huet cells, dysmegakaryopoiesis

Question 30

which classification of MDS is likely to turn into AML?

Answer 30

RAEB II- moving closer to the 20% blast count in the bone marrow is needed for an outright diagnosis of AML

Question 31

what type of disorders are myelodysplastic syndromes?

Answer 31

clonal disorders with driver mutations

Question 32

what are some of the driver mutations of myelodysplastic syndromes?

Answer 32

epigenetic mutations, RNA splicing factor mutations, Transcription factor mutations

Question 33

What are myeloproliferative neoplasms driven by?

Answer 33

mutated kinases that are constitutively active

Question 34

what happens in myeloproliferative neoplasms?

Answer 34

something in the bone marrow proliferates, neoplastic stem cells travel to other sites (like the spleen) causing extramedullary hematopoiesis, fibrosis can be apart of the disease progression

Question 35

what is chronic myeloid leukemia?

Answer 35

proliferation of predominantly mature myeloid cells

Question 36

how does chronic myeloid leukemia present?

Answer 36

peripheral leukocytosis

Question 37

what genetic aberration causes chronic myeloid leukemia?

Answer 37

the 9;22 translocation forming the BCR ABL product

Question 38

What will you see in CML patients? (3)

Answer 38

marked leukocytosis (WBC count> 100K), an increased buffy coat, splenomegaly

Question 39

What can happen to CML over time? / what are the different stages of CML?

Answer 39

chronic phase--> accelerated phase--> blastic phase

Question 40

what classifies CML being in the chronic phase?

Answer 40

when the circulating blasts are less than 10%

Question 41

what classifies CML being in the accelerated phase?

Answer 41

circulating blasts 10-19%

Question 42

what classifies CML being in the blastic phase?

Answer 42

circulating blasts >20%

Question 43

what is the myeloproliferative neoplasm of white cells called?

Answer 43

chronic myeloid leukemia

Question 44

what is the myeloproliferative neoplasm of red cells called?

Answer 44

polycythemia vera

Question 45

what is the myeloproliferative neoplasm of platelets called?

Answer 45

essential thrombocythemia

Question 46

what is the myeloproliferative neoplasm of stroma called?

Answer 46

primary myelofibrosis

Question 47

What mutations are primary myelofibrosis associated with?

Answer 47

JAK2 kinase mutations- they are the drivers for growth

Question 48

what is the effect of myelofibrosis?

Answer 48

depletion of marrow elements puts increased pressure on the spleen

Question 49

what medication is used to treat splenomegaly in a patient with myelofibrosis?

Answer 49

Ruxolitnib

Question 50

What is langerhans cell histiocytosis?

Answer 50

clonal proliferations of immature dendritic cells called langerhans cells

Question 51

what are the different forms of langerhans cells histiocytosis? (3)

Answer 51

multifocal multisystem LCH, unisystem LCH, Pulmonary LCH (smokers)

Question 52

What is the appearance of LCH?

Answer 52

grooved nuclei of the Langerhans cells: tennis-racket-shaped Birbeck granules

Question 53

What can you stain for to help identify langerhans cells?

Answer 53

S-100 and CD1a

Question 54

Where are most of the lymphocytes in the spleen located?

Answer 54

germinal centers (white pulp)

Question 55

What are four functions of the spleen?

Answer 55

phagocytosis of blood cells and blood-borne matter, antibody production, hematopoiesis, and sequestration of blood cells

Question 56

What two things could cause splenomegaly?

Answer 56

reactive splenitis and congestive splenomegaly

Question 57

what is hypersplenism and what could cause it?

Answer 57

enlargement associated with cytopenias; may be due to an issue with circulating cells themselves or due to a primary/secondary splenic disorder

Question 58

What disorders could cause splenic enlargement?

Answer 58

hereditary spherocytosis, sickle cell anemia, and idiopathic thrombocytopenic purpura (ITP)

Question 59

what occurs in hereditary spherocytosis that leads to splenic enlargement?

Answer 59

stiff red cells get stuck in sinuses

Question 60

what occurs in sickle cell anemia?

Answer 60

sickled cells are trapped

Question 61

what occurs in idiopathic thrombocytopenic purpura (ITP)?

Answer 61

platelets are opsonized, spleen clears them

Question 62

what splenic disorder could cause splenic enlargement?

Answer 62

congestive splenomegaly

Question 63

Which splenic neoplasia is more commonly seen?

Answer 63

hematologic malignancies rather than primary tumors

Question 64

What could cause splenic infarct?

Answer 64

outgrowth or clog

Question 65

What could cause Myasthenia gravis?

Answer 65

autoantibodies produced in either thymic hyperplasia or thymoma

Question 66

What are two different types of thymic pathology?

Answer 66

hyperplasia and thymoma