Peripheral Smear Review Flashcards
Systematic approach to peripheral blood smear review
Start at the feathered edge, then the zone of holes, then the zone of morphology. Check your composition in each of these regions, since some things will only appear in the feathered edge/zone of holes.
Look at platelets first, then RBCs, then white blood cells.
Then, look for other special things (inclusions, organisms, etc).
When is the zone of morphology LEAST repersentative of the blood as a whole?
When the WBC count is over 20,000
In these cases, the feathered edge is most representative.
Platelet counting in the zone of morphology to approximate platelet count
Platelet counts of 150-400 x 10^9/L are correspond to 7-20 platelets per hpf at 1000x magnification (one 100x objective field).
Spurious thrombocytopenia
Can be caused by inadequate mixing prior to analysis, activation of thrombocytes by traumatic venipuncture, or
EDTA-dependent antibodies which agglutinate thrombocytes.
Grey platelets (agranular platelets)
RBC agglutination
May be due to infection (mycoplasma pneumoniae), LPD, or plasma cell dyscrasia. May also be idiopathic.
Bite cells
Schistocytes
Only call when the cells are NOT overlapping. Should lack central pallor.
Suggests microangiopathic hemolytic anemia. Required for diagnosis fo TTP or HUS, but may not be present in DIC.
Requires emergent/urgent contact of the clinical team
Acquired spherocytosis should make you think . . .
Immune-mediated hemolysis:
Autoimmune hemolytic anemia
Cold agglutinin disease
Hemolytic transfusion reaction
Paroxysmal nocturnal hemoglobinuria
Next step is DAT (direct Coombs)
Hemoglobin C disease
Often has associated poikilocytosis
Stomatocytes
Can be seen on patients taking prochlorperazine
Howell-Jolly bodies in asplenia
Sometimes seen in megaloblastic anemia or severe hemolytic anemia
Do not over-interpret the associated poikilocytosis
Pappenheimer bodies
Lysosomes containing iron-protein complexes
Also seen in asplenia, megaloblastic anemia, or severe hemolytic anemia
Basophilic stippling
Aggregated ribosomes or polyribosomes due to incomplete or impaired RNA degradation
Seen in lead poisoning, sideroblastic anemia, myelodysplastic syndrome, thalassemias, and other hemoglobinopathies
Cabot rings
Remnants of microtubules of the mitotic spindle
Seen in severe anemia
Two main reasons to contact the clinical team immediately while reviewing peripheral smears
1: You see schistocytes
All lymphocytes from the same patient
Note the marked variation
Large granular lymphocyte
May be reactive to infection or to a tumor (including a hematopoietic tumor), may be seen in the setting of HSCT or solid organ transplant. May also represent T-LGLL or NK-LGLL.
Dasatinib therapy for Ph+ B-ALL or CML can also produce LGLs.
Use clinical judgement to consider whether or not to recommend flow.
Lymphocyte cytology in the setting of infectious mononucleosis.
Hug adjacent RBCs and have peripheral basophilia. “Skirting” with blue lines radiating from the nucleus.
Recommend EBV testing.
T-prolymphocytic leukemia
Characteristically have cytoplasmic blebs and prominent nucleoli.
Hepatosplenic T cell lymphoma
Cells have characteristic nucleoli and adjacent perinuclear hofs.
Hairy cell leukemia
Mantle cell lymphoma
Follicular lymphoma
Lymphoplasmacytic lymphoma vs plasmacytoid change in lymphocytes, which may be seen in viral infection (such as Dengue)
Chronic lymphocytic leukemia
If you have a smear with a ton of smudge cells, what can you do?
Ask the lab to repeat it with an albumin preparation
Worrisome features in monocytosis
How many lobes make a hypersegmented neutrophil?
6+
Monolobated neutrophils
Can be seen in therapy with immunosuppressants and certain antivirals:
Tacrolimus
MMF
Ganciclovir
Ddx for neutrophil hypersegmentation
B12 deficiency
folate deficiency
Hydroxyurea therapy
Methotrexate therapy
Myelodysplasia
Rarely, may be a normal variant
Anaplasmosis
Mucopolysaccharidosis
Marginal zone lymphoma cells with immunoglobulin inclusions
Look a lot like Auer rods, but the cells don’t look like promyelocytes or blasts
Jordans anomaly
Seen in neutral-lipid storage disease
Cryoglobulin inclusions
Peripheral basophilia should make you suspicious for. . .
. . . chronic myelogenous leukemia
In CML, you will see apparent left-shift but WITHOUT reactive features (no toxic granulation, no Dohle bodies)
Peripheral screening criteria for CML
WBC > 20 x 10^9/L (20,000)
Basophils > 0.2 x 10^9/L (200)
What to do when you think you see blasts on a peripheral smear
Three questions to ask yourself once you have decided there are real blasts on the peripheral smear
- Is there left-shift, or leukopenia?
- Are there auer rods / APML cytomorphology?
- Are there >20% blasts?
Typical variant APML
60-70% of cases
Low WBC count
Granules and Auer rods
Weak/absent HLA-DR
Absent CD34
Hypogranular variant APML
Minority of cases
Associated leukocytosis
Indistinct granules
Folded nuclei/sliding plates nuclei/butterfly nuclei
More typical APML cells usually sparsely admixed
May show dim CD34 or dim HLA-DR
APML on flow
APML cells. . . can have lots of granules!
SO! They can fall in the myeloid gate rather than the blast gate!
BEWARE.
Variant APML
Represents less than 5% of cases.
Lack the t(15;17) translocation.
Instead, translocations involve RARA and ZBTB16, NPM1, NUMA1, or STAT5B.
ZBTB16::RARA is the variant shown here, and has a distinct morphology. Nuclei have a more regular morphology with condensed chromatin, abundant cytoplasm, coarse granules, and fewer Auer rods.
The morphology overall looks more myelocytic. So, you have to have a high index of suspicion to look for alternative RARA translocations.
