Pathology of White Blood Cells, Lymph Nodes, Spleen, and Thymus (Part 4 of 4) Flashcards
What is acute myeloid leukemia?
mutations to hematopoietic stem cells or progenitor cells that allow for the development of a “leukemic stem cell”
What is the malignancy of in AML?
myeloid progenitors
what is the diagnostic criteria for AML?
> 20% BLASTS in bone marrow
How does AML present? (5)
fever, fatigue, bleeding/bruising, and pancytopenia
how does the peripheral blood look in AML patients?
normal/ no blasts in peripheral smear- you have to go to the bone marrow
what is the bone marrow full of in AML patients?
myeloblasts
What are the 4 ways AML can be classified?
AML with genetic aberrations, AML with MDS-like features, AML-therapy related, and AML not otherwise specified
What are the two different genetic aberrations associated with AML?
t(8;21) and t(15;17)
what does AML with t(8;21) usually show? and what are the characteristics of AML with t(8;21)
neutrophilic maturation- you can actually see the granules in the blasts; often younger patients and they have a good prognosis
What is AML with a t(8;21) genetic aberration sometimes called?
CBF leukemia
What occurs in the t(8;21) genetic aberration?
the RUNX-1-RUNX1T1 fusion product disrupts the core binding factor-mediated hematopoietic differentiation and maturation
what is AML with t(15;17) genetic aberration often referred to as?
acute promyelocytic leukemia
What is characteristic of AML with t(15;17)?
Auer rods are seen in the cytoplasm of the promyelocyte
What is the function of normal RAR?
it helps drive neutrophilic differentiation forward
what happens to the RAR in AML patients with t(15;17)?
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
What is the treatment for AML t(15;17)?
all trans RA
what are individuals with t(15;17) AML at risk for?
DIC
why are individuals with AML t(15;17) at risk for DIC?
the leukemic cells express tissue factor, which activates factor X; high levels of annexin II receptors on plasma cells convert plasminogen into plasmin
What are unusual presentations of AML?
acute monocytic leukemia (morphologic (M5) and extranodal involvement is common (including gingival and leukemia cutis)) and soft tissue mass formation
What is the soft tissue mass formation named as in a patient with AML?
granulocytic sarcoma/myeloid sarcoma/ “chloroma”
what stain is used to diagnose a granulocytic sarcoma/myeloid sarcoma/ “chloroma”?
myeloperoxidase stain
What is myelodysplastic syndrome?
a clonal disorder with morphologic manifestations that can range through many cell lineages
what is MDS considered to be a precursor to?
AML
transformation of MDS into AML is most likely when?
if MDS is due to prior cytotoxic therapy/radiation (t-MDS)
how do patients with myelodysplastic syndrome present?
cytopenias (most commonly anemia)
What is classification of MDS based on?
dysmorphic features in one or more lineages, chromosomal analysis, and if blast count is increased (but not quite to the point of AML)
What percentage of blasts gives you MDS RAEB-1?
5-9%
what percentage of blasts gives you MDS RAEB-2?
10-19%
When looking at dysmorphic features in MDS patients, what are 4 potential morphologies?
dyserythropoiesis, ring sideroblasts, pseudo pelger-huet cells, dysmegakaryopoiesis
which classification of MDS is likely to turn into AML?
RAEB II- moving closer to the 20% blast count in the bone marrow is needed for an outright diagnosis of AML
what type of disorders are myelodysplastic syndromes?
clonal disorders with driver mutations
what are some of the driver mutations of myelodysplastic syndromes?
epigenetic mutations, RNA splicing factor mutations, Transcription factor mutations
What are myeloproliferative neoplasms driven by?
mutated kinases that are constitutively active
what happens in myeloproliferative neoplasms?
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
what is chronic myeloid leukemia?
proliferation of predominantly mature myeloid cells
how does chronic myeloid leukemia present?
peripheral leukocytosis
what genetic aberration causes chronic myeloid leukemia?
the 9;22 translocation forming the BCR ABL product
What will you see in CML patients? (3)
marked leukocytosis (WBC count> 100K), an increased buffy coat, splenomegaly
What can happen to CML over time? / what are the different stages of CML?
chronic phase–> accelerated phase–> blastic phase
what classifies CML being in the chronic phase?
when the circulating blasts are less than 10%
what classifies CML being in the accelerated phase?
circulating blasts 10-19%
what classifies CML being in the blastic phase?
circulating blasts >20%
what is the myeloproliferative neoplasm of white cells called?
chronic myeloid leukemia
what is the myeloproliferative neoplasm of red cells called?
polycythemia vera
what is the myeloproliferative neoplasm of platelets called?
essential thrombocythemia
what is the myeloproliferative neoplasm of stroma called?
primary myelofibrosis
What mutations are primary myelofibrosis associated with?
JAK2 kinase mutations- they are the drivers for growth
what is the effect of myelofibrosis?
depletion of marrow elements puts increased pressure on the spleen
what medication is used to treat splenomegaly in a patient with myelofibrosis?
Ruxolitnib
What is langerhans cell histiocytosis?
clonal proliferations of immature dendritic cells called langerhans cells
what are the different forms of langerhans cells histiocytosis? (3)
multifocal multisystem LCH, unisystem LCH, Pulmonary LCH (smokers)
What is the appearance of LCH?
grooved nuclei of the Langerhans cells: tennis-racket-shaped Birbeck granules
What can you stain for to help identify langerhans cells?
S-100 and CD1a
Where are most of the lymphocytes in the spleen located?
germinal centers (white pulp)
What are four functions of the spleen?
phagocytosis of blood cells and blood-borne matter, antibody production, hematopoiesis, and sequestration of blood cells
What two things could cause splenomegaly?
reactive splenitis and congestive splenomegaly
what is hypersplenism and what could cause it?
enlargement associated with cytopenias; may be due to an issue with circulating cells themselves or due to a primary/secondary splenic disorder
What disorders could cause splenic enlargement?
hereditary spherocytosis, sickle cell anemia, and idiopathic thrombocytopenic purpura (ITP)
what occurs in hereditary spherocytosis that leads to splenic enlargement?
stiff red cells get stuck in sinuses
what occurs in sickle cell anemia?
sickled cells are trapped
what occurs in idiopathic thrombocytopenic purpura (ITP)?
platelets are opsonized, spleen clears them
what splenic disorder could cause splenic enlargement?
congestive splenomegaly
Which splenic neoplasia is more commonly seen?
hematologic malignancies rather than primary tumors
What could cause splenic infarct?
outgrowth or clog
What could cause Myasthenia gravis?
autoantibodies produced in either thymic hyperplasia or thymoma
What are two different types of thymic pathology?
hyperplasia and thymoma
