Hematopathology Quiz Part 3

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Here is the final installment of a really nice quiz one of our readers sent (check out the first and second installments).

This is a quiz recently given to medicine, pediatrics and pathology residents rotating through hematopathology. Give it a try and see how many you get right! Make sure you check out the answers and nice explanations (if I do say so myself) at the end.

1. A 24-year-old female presents with prolonged PTT which did not correct following incubation for 2 hours with control plasma. Which of the following is the most likely diagnosis?

A. Hemophilia A
B. Antiphospholipid antibody syndrome
C. Factor V Leiden

D. Von Willebrand disease

2. A “dry tap” on bone marrow aspiration can be seen in all of the following disorders EXCEPT:

A. Chronic myeloid leukemia
B. Hairy cell leukemia
C. Idiopathic thrombocytopenic purpura
D. Polycythemia vera

3. All-trans-retinoic acid is the treatment of choice for which of the following leukemias?

A. Acute promyelocytic leukemia
B. Acute lymphoblastic leukemia
C. Chronic lymphocytic leukemia
D. Chronic myeloid leukemia

4. Which of the following stains is used for supravital staining of polychromatophilic red cells?

A. New methylene blue
B. Oil red O
C. Leishman stain
D. Masson’s trichrome

5. Giant platelets are seen in:

A. Glanzmann thrombasthenia
B. Bernard-Soulier syndrome
C. von Willebrand disease
D. Thrombotic thrombocytopenic purpura

6. The leukemic cells in large granular lymphocyte leukemia are positive for:

A. CD33
B. CD 117
C. CD56
D. CD34

7. A 65-year-old female presents with fatigue. A blood smear shows abnormal lymphocytes, which are positive for CD5, CD19, and CD20, but negative for CD23. Cytogenetic analysis reveals a t(11;14). What is the diagnosis?

A. Hairy cell leukemia
B. Mantle cell lymphoma
C. Marginal zone lymphoma
D. Chronic lymphocytic leukemia

8. Serum tryptase is elevated in:

A. Hairy cell leukemia
B. Mast cell leukemia
C. T-cell acute lymphoblastic leukemia
D. Biphenotypic leukemia

Scroll down for the answers…

1. B. If you have a prolonged PTT, and you’re wondering what the cause is, one thing you can do is a mixing study, which is what this question is getting at. In a mixing study, you add a little normal plasma to the PTT (along with the patient sample) and then run the PTT again. If it “corrects” (meaning that the PTT is now normal), then it means the patient was missing something that the normal plasma provided (usually the thing that’s missing is factor VIII or IX). If it doesn’t correct (meaning that the PTT is still prolonged), then there is something in the patient sample that is inhibiting the test (usually the thing that’s inhibiting the test is an antiphospholipid antibody). So for the answers to the question: the correct answer is B (since the PTT didn’t correct). In hemophilia A, a mixing study would make the PTT correct, so A is wrong. Patients with factor V Leiden or von Willebrand disease don’t have a prolonged PTT, so C and D are wrong.

2. C. A “dry tap” means that you get the needle in the marrow cavity, and when you pull back on the syringe, no marrow is drawn out. This usually means that there is fibrosis in the marrow, which is something you can see in pretty much any myeloproliferative disorder, particularly in the end stages (so A and D could produce a dry tap). In hairy cell leukemia (B), there are little threads of fibrosis surrounding each hairy cell. It gives the marrow a “chicken-wire” appearance. Patients with ITP (C) don’t have fibrosis in the marrow. The problem in ITP is that the body is attacking its platelets – it has nothing to do with fibrosis in the marrow – so C is correct.

3. A. All-trans-retinoic acid (ATRA) is a treatment that was developed for acute promyelocytic leukemia (APL). In APL, the retinoic acid receptor is screwed up, and the malignant cells get “stuck” in the promyelocyte stage. This is not good, because if you give a patient with APL regular chemotherapy, which tends to bust open cells, you’ll release all the promyelocyte granules (which contain pro-coagulant substances), putting the patient at risk for disseminated intravasular coagulation. ATRA overcomes this maturation block, allowing the malignant promyelocytes to mature into myelocytes, then metamyelocytes, then neutrophils. Then you can give the patient regular chemotherapy without the risk of DIC. ATRA doesn’t work in any of the other leukemias listed, because those leukemias don’t have a problem with the retinoic acid receptor.

4. A. Supravital staining means that you do the stain on liquid (not fixed and dried) blood. Supravital stains are used only in certain settings, like when you’re looking for Heinz bodies, or when you’re counting reticulocytes (polychromatophilic cells). The supravital stain used to stain polychromatophilic cells is new methylene blue (A).

5. B. Both Glanzmann thrombasthenia and Bernard-Soulier syndrome are hereditary platelet disorders in which platelet receptors are deficient or defective, and patients bleed excessively. In Glanzmann, IIb-IIIa is deficient, meaning that the platelets can’t bind fibrinogen very well, which means they can’t aggregate well. In Bernard-Soulier, Ib is abnormal (meaning that platelets can’t bind von Willebrand factor very well, and can’t adhese to the subendothelium very well). It turns out that patients with Bernard-Soulier (but not Glanzmann) have big platelets, too. So B is correct. Big platelets are not seen in von Willebrand disease (C) or TTP (D).

6. C. The lymphocytes in large granular lymphocyte leukemia are T cells. They are typically positive for CD8, CD 16, and CD56 or CD57. CD33 (A) is a marker seen mostly on myeloid cells. CD117 (B) is present on hematopoietic stem and progenitor cells, and CD34 (D) is present on hematopoietic stem cells, endothelial cells, mast cells and some dendritic cells.

7. B. The t(11;14) is characteristic of mantle cell lymphoma, and not of any of the other types of lymphoma listed. Also, mantle cells tend to be CD5, CD19 and CD20 positive, but CD23 negative. The cells of hairy cell leukemia (A), marginal zone lymphoma (C) and CLL (D) have different immunophenotypes.

8. B. Mast cells contain tryptase (which is a serine protease) in their little granules. Hairy cells (A), T-cell ALL (C) cells, and the cells of biphenotypic leukemia (D) are all negative for tryptase.

Hematopathology Quiz Part 2

pencils

Here is the second of three installments of a really nice quiz one of our readers sent (the first installment is here, and the third one is coming up). This is a quiz he recently gave to his residents (from medicine, pediatrics and pathology) rotating through hematopathology. Give it a try and see how many you get right! Make sure you check out the answers and nice explanations (if I do say so myself) at the end.

 

1. Smudge cells may be seen on the peripheral blood smear in which of the following?

A. Chronic lymphocytic leukemia
B. Chronic myeloid leukemia
C. Acute myeloid leukemia
D. Thalassemia

 

2. The erythroblasts in acute erythroleukemia (AML- M6) are usually positive for which of the following?

A. PAS
B. CD71
C. CD117
D. All of the above

 

3. The rare Bombay phenotype is seen in people who have blood type:

A. O
B. A
C. B
D. AB

 

4. Cryoprecipitate contains which of the following factors?

A. Factor VIII
B. Factor IX
C. Factor II
D. Factor VII

 

5. The major hematopoietic site in the human embryo is:

A. Spleen
B. Liver
C. Kidney
D. Yolk sac

 

6. POEMS syndrome includes all of the following EXCEPT:

A. Polyneuropathy
B. Ophthalmopathy
C. M-protein
D. Skin abnormalities

 

7. The most common class of immunoglobulin produced by the malignant cells in multiple myeloma is:

A. IgA
B. IgD
C. IgG
D. IgM

 

8. Which of the following is true with respect to hemophilia A?

A. Inheritance is autosomal dominant
B. It is more common in females
C. It never manifests before puberty
D. Patients are deficient in factor VIII

 

9. The cells of which of the following have a “fried-egg” appearance on bone marrow sections?

A. Hairy cell leukemia
B. Follicular lymphoma
C. Acute promyelocytic leukemia
D. Burkitt’s lymphoma

 

10. Which of the following immunophenotypic markers is a pan-B-cell marker?

A. CD3
B. CD19
C. CD33
D. CD56

 

Scroll down for the answers…

 

 

1. A. Smudge cells (also called ghost cells or basket cells) are actually damaged lymphocytes rather than a unique type of cell. Lymphocytes are more fragile than myeloid cells (like neutrophils) – so when you make a blood smear in a patient with a lymphoid disorder (like chronic lymphocytic leukemia), there are likely to be a bunch of smudge cells.

2. D. CD71 and CD117 are both erythroid markers. Erythroblasts in AML-M6 will often stain positively with the PAS (periodic acid schiff) stain (which stains glycogen and mucopolysaccharides). Normal erythroblasts are generally not PAS positive though.

3. A. People with the Bombay phenotype don’t make H antigen. What’s H antigen, you say? It is the antigen that you make first, before you create A or B antigens. To make A and B antigens, you start with a protein precursor (sticking out of the red cell membrane). You add fucose to make what’s called the H antigen. Then, if you have the A gene, you add N-acetylgalactosamine to the H antigen, which makes it an A antigen. If you have the B gene, you add galactose to the H antigen, which makes it a B antigen. If you don’t have either A or B (in other words, if you are type O), then you just leave the H antigen as is, and you don’t make either A or B antigens.

So…people with the Bombay phenotype do not make the H antigen (they stop at the protein precursor stage). They therefore don’t make A or B antigens, either (so they are type O). If a person with the Bombay phenotype needs a transfusion, you need to find Bombay blood – because if you give any other type (regular A, B, AB or O), that blood will have some H antigen in it, and the patient will bust open all those donor red cells (not a good thing to have happen!).

4. A. Cryoprecipitate is a plasma product that contains fibrinogen, von Willebrand factor, and factors VIII and XIII.

5. D. Ok, kind of a gimme.

6. B. POEMS is a rare syndrome that includes a plasma cell dyscrasia (usually myeloma) and a bunch of other stuff. The acronym covers some of the main features: polyneuropathy, organomegaly, endocrinopathy or edema, M-protein, and skin abnormalities (including hyperpigmentation and hypertrichosis). There are other potential complications, though – and not every patient with POEMS has all five features.

7. C. The most common class is IgG. The rarest is IgM. Some people argue that an IgM myeloma doesn’t exist; others say that it exists but is super super rare. Either way, if you get a plasma cell thing that expresses IgM, the first thing you should think of is Waldenstrom’s – myeloma would be way, way down on the list.

8. D. In hemophilia A, patients are deficient in factor VIII (in hemophilia B, it’s factor IX that is deficient). Inheritance is X-linked recessive (though up to 30% of cases arise spontaneously!). As any X-linked recessive disorder, it is more common in males. It often manifests in childhood.

9. A. The hairy cells in hairy cell leukemia have been described as having a “fried egg” appearance because they have these long cytoplasmic processes (“hairs”) that push the cells apart from each other. So the little cell nuclei look like the yolks of eggs, with egg whites (cytoplasm) around them.

10. B. CD19 is a marker present on most B cells (so it’s a “pan” B-cell marker). CD3 is a T-cell marker; CD33 is a myeloid cell marker, and CD56 is a natural killer cell marker.

 

Hematopathology Quiz Part 1

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One of our readers sent in a nice quiz that he recently gave to his residents (from medicine, pediatrics and pathology) rotating through hematopathology. (more…)

How come the extrinsic and intrinsic pathways are named that way?

blue tube

Q. How did the “extrinsic” and “intrinsic” coagulation pathways get their names? It seems counter-intuitive.

A. Excellent question!! And one that a lot of students have asked in class. “Intrinsic” sounds like the important pathway that happens in the body, and “extrinsic” sounds like one that might happen in the lab, or outside the body. But that’s not at all what the names mean!

The two pathways were named that way because of the way blood clots in a test tube in the lab – not because of the way the pathways act in the body. Both pathways are totally necessary for coagulation to proceed in the body – let’s get that straight right off. But in the lab, you can do each pathway separately (the INR, or the PT, measures the extrinsic pathway, and the PTT measures the intrinsic pathway).

Extrinsic pathway

If you want to get the extrinsic pathway to run in a test tube, you have to add something extrinsic to the blood. Remember: the extrinsic pathway is kicked off by tissue factor combining with VIIa. Tissue factor is not normally present in the blood (it’s in little closed-up particles, or it’s in the subendothelium, or it’s in inflammatory cells…it’s a mysterious little substance). So if you want to get blood to clot in a test tube via the extrinsic pathway, you have to add tissue factor (which is extrinsic to the blood) to the test tube.

Intrinsic pathway

If you want to get the intrinsic pathway to run, you don’t have to add anything – everything that it needs is already in the blood. Remember: the intrinsic pathway is kicked off in the body by thrombin (and, less importantly, by other stuff, like bradykinin and high molecular weight kininogen). So everything you need for that pathway is already in the test tube; all the factors are intrinsic to the blood.

Of course, for both pathways, you have to replace the calcium and phospholipid surfaces you took out of the blood, because the coagulation factors need calcium and a phospholipid surface to work. For coagulation tests, you draw blood into a blue-topped test tube which contains a chelating substance that takes out the calcium in the blood (otherwise the blood would clot before you even got back to the lab). You also remove the platelets before running the tests (platelets provide a phospholipid surface for the coagulation factors to sit on in the body) – so you have to add back a phospholipid surface to the test tube to get the tests to run. But calcium and a phospholipid surface are normally present in the blood – so by adding them to your test tube, you’re not really adding anything new – you’re just replacing what you took out.

Ah, coagulation. Always a challenge! If you want to read a nice summary of coagulation (if I do say so myself), check out Clot or Bleed: A Painless Guide for People Who Hate Coag. It goes through both the intrinsic and extrinsic pathways, describes how they actually fit together in the body (which, strangely, is something nobody seems to talk about), and gives you a creative (if weird) way to remember which is which.

Embolus vs. thrombus

Here are a few very good questions about CNS infarcts. There are two types: red (hemorrhagic) and pale (ischemic). (more…)