A 63-year-old man from northern Wisconsin has had fever, headache and muscle aches for 5 days in June, and he removed a tick from his leg 10 days ago. Results: WBC 2.4 × 10^3/µL (2.4 × 10^9/L), platelets 64 × 10^3/µL (64 × 10^9/L), hemoglobin 13.1 g/dL (131 g/L), ALT 145 U/L (reference 7-40 U/L). On the Wright-stained film, several neutrophils contain a dark blue, stippled cluster in the cytoplasm, shaped like a mulberry. Monocytes and red cells look normal, and no stain precipitate is seen elsewhere on the slide. These inclusions are most likely:

Morulae of Anaplasma phagocytophilum

Morulae of Ehrlichia chaffeensis

Döhle bodies from the infection

Phagocytosed cocci from bacteremia

A 38-year-old man is admitted 5 hours after full-thickness burns to 40% of his body in a house fire. He has not been transfused and is afebrile. Results: hemoglobin 16.9 g/dL (169 g/L), MCV 79 fL, MCHC 37.8 g/dL (378 g/L), platelets 260 × 10^3/µL (260 × 10^9/L), PT and APTT normal. The plasma is pink and haptoglobin is 12 mg/dL (0.12 g/L). The DAT is negative. The film shows many tiny, dense round red cells, small round fragments and cells with budding projections. A health check with a CBC a year ago was normal. The red cell changes are best explained by:

Direct heat damage to the red cell membrane

Disseminated intravascular coagulation

Warm autoimmune hemolytic anemia

A 6-week-old infant with fever has a lumbar puncture that is difficult and needs several attempts. Tube 1 is bloody and tube 3 is less so. CSF from tube 3: RBC 7,800/µL (7,800 × 10^6/L), WBC 34/µL (34 × 10^6/L), glucose and protein normal for age, and no organisms on Gram stain. The cytospin shows neutrophils and lymphocytes, plus myelocytes, metamyelocytes, nucleated red cells and two megakaryocytes. The infant's CBC is normal for age, with no blasts or nucleated red cells. The immature cells in the CSF most likely came from:

Bone marrow entered during the puncture

Leukemic infiltration of the meninges

Choroid plexus and ependymal lining cells

Peripheral blood from the traumatic tap

A purple body on a red cell could be a Howell-Jolly body or a platelet lying on top of the cell. Which finding favors a platelet?

A clear halo and a fine granular texture

Visibility only after a supravital stain

A dense, smooth and perfectly round outline

Blue staining with the Prussian blue reaction

Differentials and morphology (blood and body fluids)

25 ASCP MLS practice questions on Differentials and morphology (blood and body fluids), part of Hematology. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 63-year-old man from northern Wisconsin has had fever, headache and muscle aches for 5 days in June, and he removed a tick from his leg 10 days ago. Results: WBC 2.4 × 10^3/µL (2.4 × 10^9/L), platelets 64 × 10^3/µL (64 × 10^9/L), hemoglobin 13.1 g/dL (131 g/L), ALT 145 U/L (reference 7-40 U/L). On the Wright-stained film, several neutrophils contain a dark blue, stippled cluster in the cytoplasm, shaped like a mulberry. Monocytes and red cells look normal, and no stain precipitate is seen elsewhere on the slide. These inclusions are most likely:
1. AMorulae of Ehrlichia chaffeensis
2. BDöhle bodies from the infection
3. CPhagocytosed cocci from bacteremia
4. DMorulae of Anaplasma phagocytophilum
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Answer: D · Morulae of Anaplasma phagocytophilum
Fever, leukopenia, thrombocytopenia and raised transaminases after a tick bite in the upper Midwest point to human granulocytic anaplasmosis, spread by Ixodes ticks. Anaplasma phagocytophilum grows inside neutrophils in membrane-bound vacuoles and forms these mulberry-shaped clusters, called morulae. Ehrlichia chaffeensis forms similar morulae but mainly in monocytes, and its Lone Star tick lives mostly in the south-central and southeastern US. Döhle bodies are pale gray-blue patches, and engulfed bacteria appear as separate organisms rather than one tight cluster. The film finding should be reported promptly, and PCR confirms the diagnosis.
- A: Ehrlichia chaffeensis morulae sit mainly in monocytes, and its tick is found mostly in the southern US.
- B: Döhle bodies are pale gray-blue patches, not dark stippled clusters.
- C: Engulfed bacteria appear as separate, distinct organisms rather than one mulberry-shaped cluster.
Question 2 · Hard
A 38-year-old man is admitted 5 hours after full-thickness burns to 40% of his body in a house fire. He has not been transfused and is afebrile. Results: hemoglobin 16.9 g/dL (169 g/L), MCV 79 fL, MCHC 37.8 g/dL (378 g/L), platelets 260 × 10^3/µL (260 × 10^9/L), PT and APTT normal. The plasma is pink and haptoglobin is 12 mg/dL (0.12 g/L). The DAT is negative. The film shows many tiny, dense round red cells, small round fragments and cells with budding projections. A health check with a CBC a year ago was normal. The red cell changes are best explained by:
1. ADisseminated intravascular coagulation
2. BDirect heat damage to the red cell membrane
3. CWarm autoimmune hemolytic anemia
4. DHereditary spherocytosis
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Answer: B · Direct heat damage to the red cell membrane
When red cells are heated above about 49 °C, spectrin is denatured and the membrane buds and breaks into microspherocytes and small fragments within hours of a severe burn. Loss of membrane gives the low MCV and raised MCHC, and the pink plasma and low haptoglobin show hemolysis; the high-normal hemoglobin reflects plasma loss from the burn. A negative DAT excludes warm autoimmune hemolysis, and a normal platelet count, PT and APTT exclude DIC. Hereditary spherocytosis is lifelong and would not appear suddenly after a normal CBC a year earlier. The hemolysis is usually greatest in the first 24 to 48 hours.
- A: Platelets, PT and APTT are normal, so there is no consumption of platelets or clotting factors.
- C: The DAT is negative, so there is no antibody on the red cells.
- D: Hereditary spherocytosis is lifelong; the normal CBC a year ago and the sudden onset after the burn argue against it.
Question 3 · Hard
A 6-week-old infant with fever has a lumbar puncture that is difficult and needs several attempts. Tube 1 is bloody and tube 3 is less so. CSF from tube 3: RBC 7,800/µL (7,800 × 10^6/L), WBC 34/µL (34 × 10^6/L), glucose and protein normal for age, and no organisms on Gram stain. The cytospin shows neutrophils and lymphocytes, plus myelocytes, metamyelocytes, nucleated red cells and two megakaryocytes. The infant's CBC is normal for age, with no blasts or nucleated red cells. The immature cells in the CSF most likely came from:
1. ABone marrow entered during the puncture
2. BLeukemic infiltration of the meninges
3. CChoroid plexus and ependymal lining cells
4. DPeripheral blood from the traumatic tap
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Answer: A · Bone marrow entered during the puncture
In infants the needle can enter a vertebral body during a difficult tap and carry marrow into the CSF. That explains maturing granulocytes, nucleated red cells and megakaryocytes, cells that are not present in this infant's blood. Leukemia is unlikely because there are no blasts in the CSF or the blood. Blood contamination alone would bring only the cells seen in the normal CBC. Choroid plexus and ependymal cells are lining cells that appear in tight clusters and do not include red cell precursors or megakaryocytes; the report should note marrow contamination so it is not mistaken for disease.
- B: No blasts are seen in the CSF or the blood, and the cells cover several normal stages of maturation.
- C: Lining cells form tight clusters of uniform cells and do not include red cell precursors or megakaryocytes.
- D: The infant's blood has no immature granulocytes or nucleated red cells, so blood alone cannot supply them.
Question 4 · Easy
Howell-Jolly bodies in red cells are fragments of:
1. ANuclear DNA
2. BPrecipitated iron
3. CRibosomal RNA
4. DDenatured hemoglobin
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Answer: A · Nuclear DNA
Howell-Jolly bodies are small, round, dense purple fragments of nuclear chromatin left behind when the late normoblast expels its nucleus. The spleen normally removes them by pitting, so they are common after splenectomy and in functional asplenia. They are also seen in megaloblastic anemia and severe hemolysis. Usually only one is present in a cell, often near the edge.
- B: Iron-containing granules form Pappenheimer bodies.
- C: Aggregated ribosomal RNA forms basophilic stippling.
- D: Denatured hemoglobin forms Heinz bodies, which need a supravital stain.
Question 5 · Medium
A purple body on a red cell could be a Howell-Jolly body or a platelet lying on top of the cell. Which finding favors a platelet?
1. AVisibility only after a supravital stain
2. BA clear halo and a fine granular texture
3. CA dense, smooth and perfectly round outline
4. DBlue staining with the Prussian blue reaction
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Answer: B · A clear halo and a fine granular texture
A platelet resting on a red cell usually has a faint clear halo around it and a granular purple centre, and it sits in a slightly different focal plane. A Howell-Jolly body is smooth, dense and round, lies within the cell and is usually single. Comparing the body with free platelets on the same film helps. Mistaking overlying platelets for inclusions could wrongly suggest asplenia.
- A: Bodies seen only with supravital stains are Heinz bodies or reticulum.
- C: A smooth, dense, round body is typical of a Howell-Jolly body.
- D: Prussian blue positivity identifies iron in Pappenheimer bodies.
Question 6 · Hard
During a smear review, platelets counted in 10 oil-immersion (100×) fields of the monolayer total 150. The laboratory multiplies the average per field by 20 × 10^3/µL. What is the platelet estimate?
1. A150 × 10^3/µL (150 × 10^9/L)
2. B30 × 10^3/µL (30 × 10^9/L)
3. C3,000 × 10^3/µL (3,000 × 10^9/L)
4. D300 × 10^3/µL (300 × 10^9/L)
Answer and explanation in LearnFree account
Question 7 · Hard
On one staining run, every patient's film shows gray-blue red cells and neutrophils with heavy, dark granulation that looks toxic. What is the most likely cause?
1. AToxic change from infection
2. BA buffer pH that is too low
3. CWater in the methanol fixative
4. DA buffer pH that is too high
Answer and explanation in LearnFree account
Question 8 · Medium
Cabot rings, thin red-purple loops or figure-of-eight shapes inside red cells, are:
1. AIron-containing mitochondria
2. BEarly Plasmodium ring forms
3. CRemnants of the mitotic spindle
4. DAggregates of ribosomal RNA
Answer and explanation in LearnFree account
Question 9 · Hard
A 30-year-old from Southeast Asia has lifelong hemolytic anemia with an MCV of 64 fL. After the blood is incubated with brilliant cresyl blue, many red cells show fine, evenly spaced blue-green dots that give a golf-ball look. These inclusions are:
1. AResidual ribosomal RNA network
2. BIron-loaded mitochondria
3. CDenatured hemoglobin at the membrane
4. DPrecipitated beta-chain tetramers
Answer and explanation in LearnFree account
Question 10 · Hard
Wright-stained red cells contain many small blue-purple granules spread evenly through the whole cell. A Prussian blue stain of the same blood shows no blue granules. These inclusions are best identified as:
1. ABasophilic stippling
2. BHeinz bodies
3. CPappenheimer bodies
4. DHowell-Jolly bodies
Answer and explanation in LearnFree account
Question 11 · Easy
How much of a normal red cell's diameter does the central pallor take up in a well-made film?
1. AAbout one-half
2. BAbout one-tenth
3. CAbout one-third
4. DAbout two-thirds
Answer and explanation in LearnFree account
Question 12 · Easy
Which stain confirms that small, clustered red cell inclusions seen on a Wright-stained film are Pappenheimer bodies?
1. ASudan black B
2. BCrystal violet
3. CNew methylene blue
4. DPrussian blue
Answer and explanation in LearnFree account
Question 13 · Medium
On a Wright stain, polychromatophilic red cells look slightly large and blue-gray. On a new methylene blue stain, these cells appear as:
1. ANormoblasts
2. BSpherocytes
3. CSiderocytes
4. DReticulocytes
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Question 14 · Medium
Which feature separates acanthocytes from echinocytes?
1. AOne pointed tail at a single end
2. BA few irregular spikes of uneven length
3. CA slit-like zone of central pallor
4. DMany short, evenly spaced projections
Answer and explanation in LearnFree account
Question 15 · Hard
A 19-year-old with sickle cell anemia (Hb SS) has an MCV of 86 fL. The film shows sickle cells, target cells, Howell-Jolly bodies and a few Pappenheimer bodies. The best explanation for these inclusions is:
1. APolymerization of Hb S inside red cells
2. BFolate deficiency from rapid cell turnover
3. CIron deficiency from chronic blood loss
4. DLoss of splenic function from infarction
Answer and explanation in LearnFree account
Question 16 · Medium
During a differential, a neutrophilic cell has pink secondary granules and a kidney-shaped nucleus indented less than half its width. It is counted as a:
1. APromyelocyte
2. BBand neutrophil
3. CMetamyelocyte
4. DMyelocyte
Answer and explanation in LearnFree account
Question 17 · Medium
A pleural fluid cytospin shows large cells with round, central nuclei, smooth nuclear outlines, abundant blue cytoplasm with a pale fringed edge, and clear gaps between touching cells. What are these cells most likely?
1. AMesothelial cells
2. BMacrophages
3. CPlasma cells
4. DAdenocarcinoma cells
Answer and explanation in LearnFree account
Question 18 · Hard
A CSF cytospin from an adult with a sudden severe headache shows macrophages packed with dark blue-black granules, and others holding golden-yellow crystals. What do these cells most suggest?
1. AA traumatic spinal tap
2. BBacterial meningitis
3. CCentral nervous system leukemia
4. DEarlier subarachnoid hemorrhage
Answer and explanation in LearnFree account
Question 19 · Hard
Red cells at the very thin feathered edge of a film are round and lack central pallor, but in the monolayer they are normal discs with central pallor. The correct action is to:
1. AReport spherocytes and grade them
2. BAssess morphology in the monolayer
3. COrder an osmotic fragility test
4. DAssess morphology in the thick area
Answer and explanation in LearnFree account
Question 20 · Medium
What are Döhle bodies, the pale blue patches in neutrophil cytoplasm seen in infection and burns, made of?
1. ARough endoplasmic reticulum
2. BFused giant lysosomes
3. CClumped primary granules
4. DPhagocytosed bacteria
Answer and explanation in LearnFree account
Question 21 · Hard
A 35-year-old with fever, night sweats and weight loss has an exudative pleural effusion. The cytospin differential shows 88% small mature lymphocytes, 8% macrophages, very few mesothelial cells and no malignant cells. Which cause is most likely?
1. ACongestive heart failure
2. BTuberculous pleurisy
3. CPneumothorax with effusion
4. DParapneumonic effusion
Answer and explanation in LearnFree account
Question 22 · Medium
What change in the red cell produces target cells (codocytes)?
1. AToo little membrane for its volume
2. BPolymerization of deoxygenated hemoglobin
3. CExcess membrane relative to volume
4. DA defect in membrane spectrin
Answer and explanation in LearnFree account
Question 23 · Easy
What is a red cell with one end drawn out into a single tail or point called?
1. ASchistocyte
2. BElliptocyte
3. CDacrocyte
4. DDrepanocyte
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Question 24 · Medium
Which combination of features best identifies a monocyte on a Wright-stained film?
1. AEccentric nucleus and a pale perinuclear clear zone
2. BFolded nucleus and gray-blue, ground-glass cytoplasm
3. CRound nucleus and a thin rim of sky-blue cytoplasm
4. DTwo-lobed nucleus and large orange-red granules
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Question 25 · Hard
An EDTA sample from a well outpatient with a normal WBC count and normal CRP is first examined after 30 hours at room temperature. The film shows vacuolated neutrophils with swollen, smudgy nuclei, lymphocytes with lobed nuclei and many crenated red cells. What is the most likely cause?
1. AStorage changes in the old sample
2. BToxic change from bacterial sepsis
3. CAdult T-cell leukemia/lymphoma
4. DMyelodysplastic syndrome
Answer and explanation in LearnFree account

Differentials and morphology (blood and body fluids)

Howell-Jolly bodies in red cells are fragments of:

A purple body on a red cell could be a Howell-Jolly body or a platelet lying on top of the cell. Which finding favors a platelet?

During a smear review, platelets counted in 10 oil-immersion (100×) fields of the monolayer total 150. The laboratory multiplies the average per field by 20 × 10^3/µL. What is the platelet estimate?

On one staining run, every patient's film shows gray-blue red cells and neutrophils with heavy, dark granulation that looks toxic. What is the most likely cause?

Cabot rings, thin red-purple loops or figure-of-eight shapes inside red cells, are:

A 30-year-old from Southeast Asia has lifelong hemolytic anemia with an MCV of 64 fL. After the blood is incubated with brilliant cresyl blue, many red cells show fine, evenly spaced blue-green dots that give a golf-ball look. These inclusions are:

Wright-stained red cells contain many small blue-purple granules spread evenly through the whole cell. A Prussian blue stain of the same blood shows no blue granules. These inclusions are best identified as:

How much of a normal red cell's diameter does the central pallor take up in a well-made film?

Which stain confirms that small, clustered red cell inclusions seen on a Wright-stained film are Pappenheimer bodies?

On a Wright stain, polychromatophilic red cells look slightly large and blue-gray. On a new methylene blue stain, these cells appear as:

Which feature separates acanthocytes from echinocytes?

A 19-year-old with sickle cell anemia (Hb SS) has an MCV of 86 fL. The film shows sickle cells, target cells, Howell-Jolly bodies and a few Pappenheimer bodies. The best explanation for these inclusions is:

During a differential, a neutrophilic cell has pink secondary granules and a kidney-shaped nucleus indented less than half its width. It is counted as a:

A pleural fluid cytospin shows large cells with round, central nuclei, smooth nuclear outlines, abundant blue cytoplasm with a pale fringed edge, and clear gaps between touching cells. What are these cells most likely?

A CSF cytospin from an adult with a sudden severe headache shows macrophages packed with dark blue-black granules, and others holding golden-yellow crystals. What do these cells most suggest?

Red cells at the very thin feathered edge of a film are round and lack central pallor, but in the monolayer they are normal discs with central pallor. The correct action is to:

What are Döhle bodies, the pale blue patches in neutrophil cytoplasm seen in infection and burns, made of?

A 35-year-old with fever, night sweats and weight loss has an exudative pleural effusion. The cytospin differential shows 88% small mature lymphocytes, 8% macrophages, very few mesothelial cells and no malignant cells. Which cause is most likely?

What change in the red cell produces target cells (codocytes)?

What is a red cell with one end drawn out into a single tail or point called?

Which combination of features best identifies a monocyte on a Wright-stained film?

An EDTA sample from a well outpatient with a normal WBC count and normal CRP is first examined after 30 hours at room temperature. The film shows vacuolated neutrophils with swollen, smudgy nuclei, lymphocytes with lobed nuclei and many crenated red cells. What is the most likely cause?