Lymphoma-and-CLL Flashcards

Question

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Answer 1

Basophilic stippling Hemolysis Lead poisoning Thalassemia

Answer 2

Sickle cell syndromes

Answer 3

Burr cell Uremia

Answer 4

Acanthocyte Liver disease Abetalipoproteinemia Echinocytes — Echinocytes (burr cells) are red cells with serrated edges over the entire surface of the cell, and often appear crenated in a blood smear (picture 3). The projections of the red cell membrane are smaller and much more uniform in shape and distribution in echinocytes than in acanthocytes. Acanthocytes — Acanthocytes have only a few spicules of varying size that project from the red cell surface at irregular intervals (picture 4). Spur cells appear to be the extreme form of acanthocytes and are seen in patients with severe liver disease. Causes ●Echinocytes are often found as artifacts on blood smears and have been demonstrated in both end-stage renal disease and in liver disease. ●Patients with liver disease often have acanthocytes, echinocytes, and target cells on the peripheral blood smear. Spur cells are the extreme form of acanthocytes. They are probably acanthocytes that have been additionally remodeled by an enlarged spleen and considerably enriched in cholesterol. (See 'Pathophysiology' above.)

Answer 5

Microangiopathic hemolytic anemia (e.g., TTP, DIC) Malignant hypertension Prosthetic heart valve

Answer 6

Autoimmune hemolytic anemia Hereditary spherocytosis

Answer 7

Vitamin B12 deficiency Folate deficiency Myelodysplastic syndrome Liver disease Hypothyroidism

Answer 8

``` Myelofibrosis Marrow infiltration (e.g., tumor, tuberculosis) ```

Answer 9

G6PD, unstable hemoglobinopathy

Answer 10

Myelodysplastic syndrome Stress, infection Pelger-Huët anomalyBone marrow examination with cytogenetics/FISH if myelodysplastic syndrome suspected

Answer 11

Blood smear from a patient with B cell chronic lymphocytic leukemia. The predominant lymphocytes have a very sparse cytoplasm, round to slightly oval nuclei, and no evident nucleoli. Damaged lymphocytes ("**smudge** cells") are present (arrows).

Answer 12

B12 deficiency, folate deficiency

Answer 13

Activated lymphocytes (e.g., seen in viral infection)Clinical correlation and viral serologies as appropriate; flow cytometry to rule out leukemia/lymphoma

Answer 14

Reactive bone marrow (i.e., leukemoid reaction) Chronic myelogenous leukemia Myeloproliferative neoplasm

Answer 15

Myeloblasts with Auer rod in acute myeloid leukemia ## Footnote Peripheral smear from a patient with acute myeloid leukemia. There are two myeloblasts, which are large cells with high nuclear-to-cytoplasmic ratio and nucleoli. Each myeloblast has a pink/red rod-like structure (Auer rod) in the cytoplasm (arrows).

Answer 16

RBCs should be round and the size of a **lymphocyte** nucleus, with one-**third** central pallor

Answer 17

Polymorphonuclear neutrophils (PMNs) should have three to four lobes

Answer 18

Flow cytometry: Quantitates cell surface markers and can also establish clonality

Answer 19

Polymerase chain reaction (PCR): A highly sensitive method for looking at mutations; can be qualitative or quantitative, but limited to **known mutations for which there are primers**

Answer 20

A bone marrow examination consists of two components: (1) a bone marrow **aspirate** and (2) a bone marrow **biopsy**

Answer 21

Cytogenetic analysis requires **dividing** **cells**, which are usually found only in the **marrow** (as opposed to peripheral blood); it is less sensitive than FISH or PCR but not limited by specific probes.

Answer 22

Bone marrow aspirate has a relatively low yield for evaluation of **fever of unknown origin** or aggressive **lymphoma** (excisional biopsy of an affected lymph node is preferred)

Answer 23

The bone marrow biopsy is a core biopsy that is then decalcified most helpful in determining cellularity

Answer 24

MDS The typical normal cellularity of bone marrow can be determined as 100 minus the age of the patient. Thus, this 85-year-old woman should have a cellularity of approximately 15%. A hypercellular bone marrow, macrocytosis, and pancytopenia are consistent with myelodysplastic syndrome.

Answer 25

von Willebrand disease (vWD). Explanation Remember the difference in the presentation of von Willebrand disease (mucosal bleeding) compared with clotting factor deficiencies (joint and soft tissue bleeds), except in severe vWB disease, which can mimic a factor deficiency. This is a very complex illness, divided into 3 types with 4 subtypes. Even hematologists have a difficult time interpreting the laboratory results. Know how the disease presents and what screening tests to order. Dx: Clinical suspicion + Factor 8 (low) + vWF:Ag (total vWF protein; decreased) + vWF:RCoF (ristocetin-induced agglutination of normal platelets; decreased) + RIPA (ristocetin-induced agglutination of patient’s platelets; decreased). Tx: Depends on the form of vWD; mainstay is desmopressin (DDAVP®).

Answer 26

Tx: Phlebotomy to keep Hct \< 45% ± myelosuppression (hydroxyurea) + aspirin for vasomotor symptoms. Dx: There is no diagnostic consensus, but most patients have increased red cell mass + normal pO2 + exclusion of CML, ET, and myelofibrosis + hypercellular marrow with increased megakaryocytes. Tx: Phlebotomy to keep Hct \< 45% ± myelosuppression (hydroxyurea) + aspirin for vasomotor symptoms.

Answer 27

alpha thalassemia trait. ## Footnote Explanation The chronic mild anemia and low MCV is concerning for iron deficiency, yet iron studies do not reveal iron deficiency. Thalassemias cause mild anemias with a low MCV and are often misdiagnosed as iron deficiency. A normal Hgb electrophoresis in the setting of a microcytic anemia and the exclusion of iron deficiency allows you to diagnose α-thalassemia. Giving the patients iron long-term results in an iron overload state. It is difficult to diagnose hemochromatosis in someone who takes exogenous iron. Dx: Clinical + diagnosis of thalassemia + normal iron studies + increased ferritin. Tx: Discontinue iron supplements.

Answer 28

MGUS, review in 6 months The normal labs and exam in this man suggest that he has a monoclonal gammopathy of undetermined significance, with a rate of progression to myeloma of approximately 1% per year. A high percentage of elderly people have a monoclonal gammopathy, and it is not necessary, prudent, or efficient to evaluate all such people with a bone marrow examination. Patients with an M-spike greater than 1.5 g/dL, a non-IgG monoclonal gammopathy, an abnormal free light chain ratio, or evidence of end-organ damage warrant a bone marrow examination.

Answer 29

Splenectomy

Answer 30

Dx: Clinical (including FH of hemolytic anemia) + spherocytes on peripheral smear + osmotic fragility test (abnormal). Tx: Folate + iron and folic acid, perhaps supportive blood transfusions, and possibly splenectomy (total or partial).

Answer 31

delayed hemolytic transfusion reaction. Explanation Note the presence of hemolysis, as reflected by the increase in the I. bili, but the event occurred 1 week after transfusion. This phenomenon is usually due to Rh incompatibility or minor antigen mismatches that result in the formation of low levels of antibodies after the original transfusion (such a low level that the cross-matching process does not pick them up). Anamnestic production of antibody occurs with subsequent transfusion. Most cases do not result in symptomatic hemolysis; this presentation is an extreme case. Dx: Clinical + evidence of hemolysis (increased LDH and indirect hyperbilirubinemia + low haptoglobin and positive Coombs test) + blood bank evaluation of pre- and post-transfusion samples with repeat cross-matching. Tx: Usually supportive care is adequate.

Answer 32

Diagnosis is febrile nonhemolytic transfusion reaction. Explanation This is not an acute hemolytic transfusion reaction because the lab tests do not indicate hemolysis. Dx: Clinical; exclude other causes of fever and exclude hemolysis. Tx: Antipyretic ± meperidine for rigors

Answer 33

Diagnosis is B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Explanation This disease can present as a chronic leukemia or as an indolent lymphoma. B-cell CLL has a bimodal age distribution: ≥ 70 years and between 30 and 39 years. Autoimmune hemolytic anemia and thrombocytopenia often occur. Most patients do not have the exaggerated response to mosquito bites, but this is 1 diagnosis to consider when you see such a response. Dx: Monoclonal B-cell lymphocytosis (CD5+) or expansion of the marrow with the same cells. Tx: Observation in early stage ± localized radiation therapy ± treatment options that include single-agent therapy with and combinations of chlorambucil, fludarabine, bendamustine, pentostatin and rituximab.

Answer 34

rolonged PTT is Factor 12 deficiency. Explanation Suspect Factor 12 deficiency when you see a prolonged PTT without any history or clinical evidence of bleeding. It is not associated with a clinical bleeding disorder. The correction with the 1:1 mix tells you that an inhibitor is not the cause (an inhibitor would not correct with the mix). Dx: Clinical + PT/PTT + 1:1 mix with normal plasma (corrects). Tx: No treatment indicated.

Answer 35

primary myelofibrosis (MF). Explanation While myeloproliferative disorders can have splenomegaly (e.g., polycythemia vera [PV] and essential thrombocytosis [ET]), think about myelofibrosis (splenomegaly present in ∼ 90% of patients) when a case describes massive splenic enlargement. Hepatomegaly is also seen in ∼ 50% of patients. Marrow biopsies are difficult (resulting in a “dry tap”) because of the fibrosis, but some patients in early stages have hypercellular marrows with scant fibrosis. Buzzwords for this presentation are as follows: massive splenomegaly, teardrops, and dry tap. Dx: Clinical + exclude other myeloproliferative disorders. Tx: Transfusion support.

Answer 36

autoimmune hemolysis due to Mycoplasma infection. Explanation Remember the classic association between cold autoimmune hemolytic anemia (AIHA) and Mycoplasma and EBV infections. Dx of autoimmune hemolysis: Clinical + Hgb (low) + evidence of hemolysis (increased indirect hyperbilirubinemia, reticulocyte count, and LDH; decreased haptoglobin) + positive Coombs test (C3 type = complement Coombs test). Tx: Supportive (+ treat underlying Mycoplasma infection).

Answer 37

Bernard-Soulier syndrome. Explanation Thrombocytopenia, giant platelets on the smear, and the prolonged bleeding time are the clues to Bernard-Soulier, a.k.a. giant platelet syndrome. The defect is absence of the GP1b-9-5 receptor. This is not von Willebrand’s because the labs are not right for that diagnosis (Factor 8 is often low and bleeding time is prolonged, and no giant platelets are seen). Dx: Rare syndrome that is difficult to distinguish among other congenital platelet disorders (gray platelet syndrome, May-Hegglin anomaly, and some types of vWD); diagnosis is within the realm of the hematologic subspecialist. Tx: Platelet transfusions prn.

Answer 38

Diagnosis is acute splenic sequestration. Explanation Note that patients with SS sickle cell anemia autoinfarct their spleens in infancy, so they are not at risk for this presentation as adults. Patients with the milder SC disease, however, are at risk. Dx: Clinical + reticulocytosis. Tx: Red cell transfusion with splenectomy as a last resort.

Answer 39

heparin-induced thrombocytopenia (HIT). Explanation Clinical scenario could present an in-house patient who develops thrombocytopenia while on heparin. Highest risk of clots, however, is after the thrombocytopenia resolves, usually after the heparin has been discontinued. Recognize that platelets can be in the normal range if the patient had a thrombocytosis at the initiation of heparin. Dx: Clinical (prediction models, such as the 4 Ts, are helpful) ± serotonin release assay (positive) or solid phase immunoassay (negative test excludes). Tx: Stop heparins + lepirudin (do not use in patients with low GFR), argatroban, or fondaparinux + warfarin (after platelets rise to \> 150,000) and overlap with alternative anticoagulation x 5 days.

Answer 40

acute hemolytic transfusion reaction. The most likely cause is ABO incompatibility. Explanation Anytime a patient has fever during a transfusion, consider this first. Dx: Clinical + evidence of hemolysis (increased LDH and indirect hyperbilirubinemia + low haptoglobin and positive Coombs test) + blood bank evaluation of pre- and post-transfusion samples with repeat cross-matching. Tx: Stop transfusion immediately + IVF support + furosemide-induced diuresis + monitoring for DIC (check PT/PTT, fibrinogen, fibrin degradation products, and D-dimer).

Answer 41

5q myelodysplasia. Explanation This subset of myelodysplasia is worth remembering because most patients are women and have a favorable prognosis. The 5q is a big clue, as is the thrombocytosis (not thrombocytopenia, as in most cases of myelodysplasia). These patients often respond favorably to lenalidomide and have increased survival compared with other myelodysplasias. Pseudo-Pelger—Huet cells (buzzwords to remember!) are seen in myelodysplastic states in which the granulocytes have decreased segmentation. Dx: Anemia + preserved or increased platelets + lack of blasts + marrow cells with 5q31 deletion. Tx: Lenalidomide.

Answer 42

Pseudo-Pelger—Huet cells

Answer 43

loss of vitamin K-producing organisms in the gut due to use of broad-spectrum antimicrobials. Explanation Certain cephalosporins can also do this when their side chain antagonizes vitamin K. Dx: Clinical. Tx: Stop the offending antimicrobial.

Answer 44

chronic myelogenous leukemia (CML). Explanation The major clue here is the presence of the Philadelphia chromosome, the BCR-ABL translocation [t(9;22)], and the excess of granulocytes in various stages of development. Although it has poor sensitivity and specificity, the low LAP score may help you distinguish CML from a leukemoid reaction and polycythemia vera, both of which have increased LAP scores. If you see the same sort of presentation with low platelets, think more of myelodysplasia, not myeloproliferative disease. Remember: This is not acute leukemia because the peripheral blood contains a spectrum of differentiated granulocytes, and acute leukemia is marked by maturation arrest and overproduction of blasts. Acute leukemia is defined by \> 20% blasts in the marrow. Dx: Leukocytosis with excess myeloid cells + evidence of Philadelphia chromosome (the chromosome itself, evidence of the BCR-ABL fusion gene, or evidence of the BCR-ABL mRNA). Tx: Based on phase and patient’s age; chronic and early accelerated phase is treated with a tyrosine kinase inhibitor; e.g., imatinib. Refractory and nonresponsive patients are treated with stem cell transplant.

Answer 45

thrombotic thrombocytopenic purpura (TTP). Explanation This diagnosis is caused by ADAMTS13 deficiency. Recognize the classic features: fever, anemia (microangiopathic hemolytic), renal failure, thrombocytopenia, and CNS disease. (It is rare that all 5 manifestations are present in the clinical setting). Also recognize that the clinical scenario could include: a pregnant woman, h/o autoimmune disease (especially lupus), h/o metastatic cancer (especially adenocarcinomas), h/o certain chemotherapy agents, h/o post-stem cell transplant, or no symptoms (healthy patient). The presentation is similar to malignant hypertension and scleroderma renal crisis, but hypertension is not a feature in TTP. Dx: Clinical + Required features: thrombocytopenia and microangiopathic hemolytic anemia (schistocytes) + PT/PTT (normal). Tx: Immediate plasma exchange transfusion

Answer 46

antiphospholipid syndrome (APS). Explanation The PTT in APS is sometimes considered “paradoxically prolonged” because the disease causes venous thrombosis, not bleeding. Dx: Use clinical classification criteria (needs 1 clinical criterion [thrombosis or pregnancy morbidity] + 1 laboratory criterion [anticardiolipin antibody, anti-β2-glycoprotein 1 antibody, or lupus anticoagulant]), with repeat laboratory criteria assessed 12 weeks later. Tx: Acute DVT is treated with a heparin product followed by indefinite lifetime anticoagulation with warfarin.

Answer 47

acute hemolysis due to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Explanation The history of infection prior to development of acute hemolysis is important and, together with characteristic “bite cells,” usually suggests the diagnosis. The negative Coombs test makes infection-associated autoimmune hemolytic anemia unlikely. Dx: Clinical + measurement of serum G6PD 3 months after the acute hemolytic event. If done earlier, the G6PD level may be inappropriately high because reticulocytes formed in response to the hemolysis contain high levels of the enzyme. Tx: Specific treatment depends on the type and extent of disease; all patients should avoid certain drugs that trigger hemolysis (e.g., dapsone, nitrofurantoin, primaquine, sulfa drugs, rasburicase) and eating fava beans.

Answer 48

β-thalassemia minor. Explanation Both α- and β-thalassemia are associated with microcytic anemias, but β-thalassemia is the one with the abnormal hemoglobin electrophoresis (increased A2 component). Dx: Clinical and of exclusion (exclude iron deficiency anemia) + Hgb electrophoresis (increased HbA2, perhaps presence of HbF, and in severe thalassemia there is no Hgb A production). Tx: None required; discontinue iron supplementation if appropriate. Show Question

Answer 49

acquired methemoglobinemia due to inhalation of nitrites. Explanation Remember the association between inhalation of amyl nitrite (slang terms = “poppers,” “rush,” “jungle juice”) and methemoglobinemia. Dapsone and local anesthetics are also associated with acquired methemoglobinemia. Dx: Clinical (high suspicion if cyanotic and normal oxygenation) + arterial methemoglobin concentration. Tx: Varies depending on etiology and concentration. For acquired cases with \> 20% methemoglobin concentration, give methylene blue.

Answer 50

anaphylaxis to blood products. Explanation Patients with selective IgA deficiency can develop anti-IgA antibodies. When given blood products containing IgA, anaphylaxis can result. Definitely remember that anaphylaxis is a possibility if IgA-deficient patients are given routine blood products. Dx: Clinical. Tx: Stop the transfusion immediately + IV fluids + epinephrine ± glucocorticoids.

Answer 51

aplastic anemia caused by sulfa drug. Explanation If the patient were not taking TMP/SMX, a drug notoriously associated with aplastic anemia, the differential diagnosis would reasonably include myelodysplasia, myelofibrosis, paroxysmal nocturnal hemoglobinuria (PNH), and aplastic anemia due to viruses such as HBV. Other drugs that can cause aplastic anemia include valproic acid, phenytoin, NSAIDs, chloramphenicol, carbamazepine, and nifedipine. Dx: Clinical (but bone marrow aspiration and biopsy may be performed). Tx: Discontinuation of marrow-suppressing drug.

Answer 52

Factor 8 inhibitor. Severe bleeding, high titer inhibitor – For patients with higher titer factor VIII inhibitors (ie, ≥5 Bethesda units) and/or severe bleeding, we suggest the use of an activated prothrombin complex concentrate (aPCC; eg, factor VIII inhibitor bypassing activity [FEIBA]) or recombinant human factor VIIa [45,46]. Human factor VIII products generally cannot be given in high enough amounts to overcome the inhibitor. RecomExplanation The bleeding and the prolonged PTT suggest a factor deficiency. The failure of the PTT to correct with the mixing study tells you that an inhibitor is present. You might have been thinking this was antiphospholipid syndrome (APS), which is associated with prolongation of PTT and does not correct with the mixing study. But remember that APS is associated with clotting, not bleeding. This is not von Willebrand’s because the bleeding time is normal and the mixing study does not correct (it does correct in von Willebrand’s disease when Factor 8 is replaced). Remember conditions associated with development of Factor 8 inhibitors: age \> 50 years, pregnancy, RA, SLE, and underlying malignancy. Dx: Clinical + PTT (prolonged) + 1:1 mix (fails to correct). Tx: DDAVP® (desmopressin) ± Factor 8 concentrate for severe bleeds + immunomodulation to remove the inhibitor (systemic corticosteroids, steroids + cyclophosphamide, steroids + rituximab, or IVIG).

Answer 53

anemia is inflammation (sometimes called anemia of chronic disease [ACD]). Explanation Note that this anemia can occur with any chronic disease, such as rheumatoid conditions, chronic infections, and cancers. Dx: Iron studies (serum Fe, TIBC, ferritin, Fe/TIBC) ± soluble transferrin receptor assay. Tx: Treat underlying condition.

Answer 54

Broad-spectrum antibiotics eradicate the vitamin K-producing organisms from the intestine and lead to deficiency. Dx: Clinical + PT (prolonged) + platelets (normal). Tx: Support and discontinuation of antibiotic or change to an antibiotic with a more narrow spectrum of activity + vitamin K replacement.

Answer 55

The 2 thrombophilias are activated protein C (APC) resistance and prothrombin gene mutation. Explanation APC resistance is the disease caused by Factor 5 Leiden mutation. The G20210A mutation is the mutation in the prothrombin gene. Dx: Clinical suspicion + functional assay + gene testing. Tx: Anticoagulation.

Answer 56

ron deficiency anemia (IDA).

Answer 57

DIC in the setting of acute promyelocytic leukemia (aPML or AML M3 type). Explanation This script includes a coagulopathy due to the presence of disseminated intravascular coagulation (DIC), which is most commonly seen in aPML. This is an important script to remember: When AML M3 presents with DIC, urgent prescription of an all-trans retinoic acid (ATRA) drug is necessary because aPML is 1 of the most malignant forms of AML (even though it is also 1 with the best prognosis when treated). The t(15;17) translocation is 1 of the molecular clues to the diagnosis of aPML. Dx: CBC or marrow biopsy showing characteristic promyelocytes ± Auer rods + flow cytometry/cytogenics + evidence of DIC. Tx: Immediate ATRA-based chemotherapy.

Lymphoma-and-CLL Flashcards

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