Hematopathology Flashcards
Name the AML with recurrent genetic abnormalities that is associated with myeloblasts, monoblasts, promonocytes, and eosinophils with basophil-like granules? (favorable prognosis)
What coexisting mutation moves this leukemia from a favorable prognosis to an intermediate one?
AML with inv(16)(p13.1q22), CBFB-MYH11 fusion
KIT mutation
Name the AML with a favorable prognosis with monocytic differentiation and blasts that do not express CD34?
What coexisting mutation in this type moves it to a worse prognosis?
AML with mutated NPM1
FLT3-ITD
Name the AML with increased blasts and abnormal promyelocytes ?
What is the feared complication of this disease?
Describe the morphology of the two subtypes?
APL with t(15;17)(q22;q21) PML-RARA
Life-threatening coagulopathy with DIC
Hypergranular- Blasts with bilobed or convoluted nuclei, marked thrombocytopenia, abnormal promyelocytes with large granules
Hypogranular- Blasts with bilobed nuclei (sliding plates) and absent cytoplasmic granules
Name the AML with abnormal neutrophils with salmon-colored granules and dysplastic nuclear features?
What kind of prognosis does this have?
What confers a worse prognosis?
What is unique about the Auer rods in this disease?
What other disease is this associated with?
AML with t(8;21)(q22;q22) RUNX1-RUNX1T1
Favorable
Intermediate risk
They are long and thin with tapered ends
Systemic mastocystosis
Describe the molecular change associated with Follicular Lymphoma?
t(14;18)(q32;q21) BCL2-IGH
BCL2 is 18q21 and IGH is on chromosome 14
Name the AML with recurrent genetic abnormalities with a intermediate prognosis with mainly monoblasts and promonos in the peripheral blood containing azurophilic granules?
AML with t(9;11); MLLT3-KMT2A
Name the three AMLs with defining cytogenetics abnormalities (That is, if you have the abnormality, it has to be AML)
t(8;21), inv(16), t(15;17)
Name the four main differential diagnosis with microcytic anemia?
Iron deficiency anemia
Anemia of chronic disease
Thalessemia
Sideroblastic anemia
What does MCV stand for?
Mean cell volume
What does MCH stand for? Describe it!
What about MCHC? Describe it!
Mean corpuscular hemoglobin
The average amount of hemoglobin in a RBC
Mean corpuscular hemoglobin concentration
Hemoglobin concentration in a given volume of red cells
What is the physiological mechanism behind iron being stuck in the macrophage in anemia of chronic disease/inflammation?
Hepcidin blocks ferroportin in the macrophage, iron is stuck
Where is iron trapped in sideroblastic anemia?
The mitochondria
Describe ferritin in the context of an iron panel
Ferritin is a special storage protein that can squirrel iron away from pathogens. The level is increased in reactive conditions such as anemia of chronic disease, and decreased in iron deficiency anemia (you don’t want to store the little iron you have left)
Describe TIBC and transferrin in the context of an iron panel
TIBC measures the body’s ability to bind iron with transferrin. In iron deficiency anemia, this value is high as the liver produces more transferrin to maximize the little iron available.
In anemia of chronic disease, the TIBC is low as the body produces less transferrin and more ferritin (ferritin helps keep the iron away from bugs)
describe iron level in the context of an iron panel. What does a decreased level mean? Increased?
The iron level is a measure of the amount of iron bound to transferrin and is non-specific due to a considerable variation from person to person due to diet. Decreased levels are associated with both iron deficiency and anemia of chronic disease (does not measure iron bound to ferritin).
Increased levels can be associated with iron overload
Describe % transferrin saturation in the context of an iron panel?
This measures the percentage of transferrin that has iron bound to it. In iron deficiency anemia this level should be low as you have lots of transferrin but little iron. In anemia of chronic disease this value is typically normal. This is because the body is producing less transferrin and there is some iron around, it’s just that a lot of it is bound to ferritin.
What is sideroblastic anemia?
What is it’s most common cause?
What genetic syndrome is it associated with and how is this inherited?
Abnormalities in porphyrin blocks heme synthesis, iron gets stuck in the mitochrondria.
Alcohol
Erythroid specific ALA synthase (x-linked)
*Bonus, can also be associated with MDS
What does the iron panel look like in thalassemia minor?
What Hbg electrophoresis value will be changed? Increased or decreased?
Normal
HbA2, increased
Define megaloblastic anemia…
What is an interesting feature of the bone marrow in this condition?
Dysplasia
What is the common cause of B12 deficiency? Main clinical finding? Time of onset?
What is the common cause of folate deficiency?
Neurological symptoms? Time of onset
Anything causing malabsorption (pernicious anemia, etc..)
Neurological symptoms
Long time of onset
Decreased intake (leafy gree vegetables)
No, no neurological problems
Shorter time of onset
What happens to the levels of homeocytstein and MMA in folate deficiency?
In B12 deficiency?
Homecystein is increased and MMA is normal in folate deficiency
Both homocystein and MMA are increased in B12 deficiency
What is pernicious anemia?
What is the most specific antibody?
The most sensitive?
Autoimmune disorder with anti-intrinsic factor and anti-parietal cell antibodies. These cause chronic atrophic gastritis.
Anti-intrinsic is most specific (Intrinsically specific!)
Anti-parietal is most sensitive
The Schilling test is used for ____ not for ____
What is the concept?
Determine the cause of B12 deficiency, not to diagnose it
You give B12 with and without intrinsic factor and see if B12 is in the blood stream. If B12 alone is low and it’s normal with IF administration then you have pernicious anemia, if it is low and still low with IF then you either have malabsorption or bacterial overgrowth
Hemolytic anemia is defined as….
The abnormal breakdown of RBCs
What stain can be used to highlight reticulocytes?
Supravital blue stains like methylene blue
How are spherocytes formed?
What is the most common mutation in the hereditary form of spherocytosis?
RBCs lose some of their surface membrane, causing them to be unable to make the biconcave shape, and instead make a simple sphere.
Ankrin
How are eliptocytes formed?
In order to diagnose hereditary eliptocytosis you need to have what percentage of eliptocytes?
They have cytoskeleton defects which prevent them from reforming their normal shape after squeezing through the capillaries.
> 25% eliptocytes
Hereditary stomatocytosis is inherited in what manner? What defect is it associated with?
What other three conditions is it associated with?
AD
Defect in the Na/K permeability of RBC membrane
Alcohol, liver disease, Rh null disease
What is a Heinz body? Bite cell?
What conditions are they associated with?
RBC inclusions made of hemoglobin
Bite cells are RBCs missing part of their membrane corresponding to where a Heinz body was removed by the spleen
Associated with G6PD deficiency and hemoglobin problems (unstable hb, alpha thal with Hb Barts or H)
What does G6PD help with?
Prevents oxidative damage of the red cells via the pentose phosphate pathway
How is G6PD inherited?
X-linked
Echinocytes can be seen in what genetic abnormality? How is in inherited?
Pyruvate kinase deficiency
Autosomal recessive
What are the four main conditions associated with acanthocytes?
Liver disease
Post splenectomy
McCloud Syndrome
(weak kell antigens)
Abetalipoproteinemia (mutated microsomal triglyceride transfer protein, can’t absorb fat from food)
What state is iron in in Methemoglobins?
3+ (ferric) state
Name the lanes from positive to negative in an alkaline gel?
Acid gel?
A F S C
A fat santa claus
F A S C
For a safe christmas
HbA is composed of what types of chain(s)?
HbA2?
HbF?
Alpha2Beta2
Alpha2Delta2
Alpha2Gamma2
What is considered a “fast moving” hemoglobin on alkaline gel? Name 4
What is considered a “slow moving” hemoglobin on alkaline gel? Name 1
Fast moving are at the positive end
Hb N, I, H and Barts (from the NIH!)
Slow moving are at the negative end
Constant Spring
What runs in the C lane on Alkaline Gel? (4)
A CEO
HbA1, HbC (duh), HbE, HbO
What runs in the S lane on alkaline gel?
5
HbS, HbD, HbG, HbLepore, hasharon
LSD G!!!
Sickle cell disease is caused by…. (genetically)
Associated with what carcinoma?
A point mutation in the Beta-globulin chain (glutamic acid replaced by valine)
Renal medullary carcinoma
What percentages of Hb should you have in sickle cell disease? Sickle cell trait?
HbS >80%, HbF <20%, HbA2 <4%, HbA =0
HbS 35-45%, HbF <2%m Hb A2 <4%, HbA 50-60%
What does the morphology look like in the peripheral smear with sickle cell trait?
Normal
What does the morphology look like in the peripheral smear with Hemoglobin C trait? Disease?
Target cells and crystals
Target cells and crystals (the same)
What is the level of HbC in HbC trait? Disease?
50%
90%
What is the physiological process behind the formation of target cells?
Too much cell membrane (opposite of spherocytes)
Where do patients with HbE disease typically come from?
What lane does HbE run with on alkaline gel?
SE Asia
C (A CEO)
What is HbH composed of? HbBarts?
What thalassemia are they associated with?
Beta(4) tetramers, gamma (4) tetramers
Alpha thalassemia
Hemoglobin H forms what types of inclusion?
Golf-ball like inclusions
What are the clinical symptoms of beta thalassemia minor? Intermedia? Major?
Minor- Asymptomatic with mild anemia
Intermedia- Anemia but not transfusion dependent
Major- Severe anemia, transfusion dependent
What is paroxysmal nocturnal hemoglobinuria?
An acquired anemia due to a mutation that disrupts a protein in red cell membranes. This protein usually halts complement activation on red cells, and without it they are lysed intravascular.
What is the gene mutation involved in paroxysmal nocturnal hemoglobinuria? What does it encode?
How can flow cytometry be used to detect this disease?
What is a classic test for this condition?
PIG-A, the GPI Anchor protein
Can look for the loss of GPI linked proteins
The HAM acidified serum lysis test
Name the laboratory test that can be used to detect paroxysmal nocturnal hemoglobinuria?
How does it work?
The HAM acidified serum lysis test
Placing red blood cells in mild acid, they will lyse if they lack the proper enzyme
What is a Howell-Jolly body?
What condition is it associated with?
A single dense inclusion in RBCs made of DNA
Seen post-splenectomy or auto-splenectomy
What is basophillic stippling?
What conditions is it seen in?
Multiple blue dots composed of RNA
Lead poisoning, pyrimidine 5` nucleotidase deficiency
What is a pappenheimer body?
What conditions is it associated with?
An inclusion in an RBC made of iron. Can be seen in iron overload and post splenectomy
What tick infection is associated with babesia?
Where are the parasites located?
Ixodes spacularis
Inside and outside the red cells
What is the mutation in Chediak Higashi syndrome? What does this cause?
What cells are effected by this?
CHS1 (LYST): Causes a defect in the lysosome formation causing decreased phagocytosis and microtubule polymerization
Cells with granules, PMNs, LGLs, neurons, platelets
Causes issues with those cell lines
What are MYH9 related disorders?
How are they inherited?
What are they characterized by?
AD inherited disorders with large platelets but decreased overall platelets (thrombocytopenia), hearing loss, cataracts, WBCs with Dohle bodies, and glomerulonephritis
What is Alder Reilly anomaly?
What morphologic feature is present in the WBCs in this disorder? How are the PMNs effected mechanically?
How is it inherited?
Lack the lysozymal enzymes to break down mucopolysaccarides
Dense azurophillic granules in ALL WBCs
No effect on function
AR
Pelger-Huet anomaly is associated with what mutation?
What is the inherited form associated with clinically?
Lamin B receptor mutation
No clinical significance
Contrast the macrophage morphology in Gaucher disease vs Niemann-Pick disease?
What deficiencies is each associated with respectively
Gaucher- Tissue paper cytoplasm with wrinkles, glucocerebrosidase deficiency
NP- Foamy vaculated cytoplasm, sphinomyelin deficiency
What are the diagnostic criteria for LGL leukemia?
> 6 months with >2000 cells
What are the 4 markers commonly expressed in hematogones?
What marker can help distinguish this from B ALL?
CD10, CD20, CD34, Tdt
B ALL should NOT have CD10
What markers are associated with immature hematopoietic cells?
Myeloid cells?
Monocytic cells?
Megakaryocytes?
Immature- CD34, CD117, TdT
Myeloid: CD13, CD15, CD33
Monocytes: CD4, CD11b, CD14, CD24, CD64, CD68
Megakaryocytes: CD41, CD42, CD61
