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Leukemia Information and Courses from MediaLab, Inc.

These are the MediaLab courses that cover Leukemia and links to relevant pages within the course.

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Cerebrospinal Fluid
The cells present in this field may indicate what condition?View Page
Which of the following statements is true about the cells shown at the right?View Page
More Blast Cells

Four blast cells are seen in this field. Notice the smooth chromatin pattern, nucleoli, high NC ratio and irregularly shaped nuclei. These blasts were observed in a spinal fluid sample from a patient with acute lymphocytic leukemia.

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Malignant Cells

Malignant cells that have broken away from a tumor within the brain or meninges may also be present in spinal fluid. Tumor cells may be difficult to distinguish from macrophages or pia arachnoid mesothelial cells. While blasts in the CSF also indicate malignancy, in particular leukemia, for the purposes of this discussion, they are considered separately.

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Match the condition on the left with associated cells on the right.View Page
Blast Cells

Blast cells may be seen in the spinal fluid when cell proliferation in acute leukemia or lymphoma spreads to the central nervous system. The arrows indicate the two blasts in this field. Notice the smooth chromatin pattern in the nucleus and prominent nucleoli in both cells. Notice that an Auer rod is present in the cytoplasm in the blast to the right. The Auer rod indicates that these blasts are myeloblasts rather than lymphoblasts. A segmented neutrophil and several red cells can also be seen.

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CLIA Blood Banking Review
Unexpected positive reactions encountered during forward ABO typing may be due to:View Page
HLA antigen testing may be used for all except the following:View Page

CLIA General Laboratory Review
A patient with atypical (reactive) lymphocytes in his peripheral blood smear should be tested for:View Page

CLIA Hematology / Hemostasis Review
Which of the following conditions might give rise to the red cell abnormality depicted here:View Page
What is the cell indicated by the arrow in this illustration:View Page
The cell indicated by the arrow in this illustration is called:View Page
The WBC indicated by the arrow in this illustration is exhibiting:View Page
Identify the object contained in the cell in this illustration indicated by the arrow:View Page
Which of the following methods is not used to classify acute leukemia:View Page
The procedure which may be used to assist in differentiating chronic myelocytic leukemia from leukemoid reaction is:View Page
Flow cytometry is not a useful tool in the study of this disorder:View Page
Match the clinical findings with the associated type of leukemia:View Page

Confirmatory and Secondary Urinalysis Screening Tests
Heat and Acid Test for Urinary Protein

The heat and acetic acid test is another semiquantitative test used to confirm the presence of protein in urine. It is more sensitive than the SSA test because the pH of the sample is brought close to the isoelectric point of proteins. However, this test is sometimes considered too sensitive because it can detect trace amounts of protein which are considered normal. The heat and acetic acid test gives false positive results with inorganic iodides, benzoin, tolutamide, and proteoses, similar to the SSA test. Bence-Jones protein consists of dimers of either kappa or lambda light chains from immunoglobulins. This abnormal protein is most often associated with multiple myeloma, but can also be found in cases of lymphoma, macroglobulinemia, leukemia, and other malignancies (Balant and Fabre, 1978). Testing for Bence-Jones protein is not part of the routine urinalysis. However, if Bence-Jones protein is suspected, the heat precipitation test or immunoelectrophoresis can be performed on a urine specimen. The heat precipitation test is based on the protein’s unusual solubility properties. Bence-Jones protein precipitates at temperatures between 40ºC and 60ºC (56ºC optimum), but dissolves again at 100ºC. Upon cooling, the precipitate will reappear around 60ºC and will dissolve again below 40ºC

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Erythrocyte Inclusions - Wright Stained Smears
Cabot rings may be seen in rare occasions in patients who have:View Page
Coarse basophilic stippling is usually seen in patients who have:View Page

Introduction to Bone Marrow
Bone marrow examinations may aid in the diagnosis of:View Page
Normal M:E Ratio

The normal M:E ratio in adults varies from 1.2:1 to 5:1 myeloid cells to nucleated erythroid cells. An increased M:E ratio (6:1) may be seen in infection, chronic myelogenous leukemia or erythroid hypoplasia. A decreased M:E ratio (<1.2-1) may mean a decrease in granulocytes or an increase in erythroid cells. M:E ratios are somewhat higher in newborns and infancy than in later childhood and in adults. It is important to note that lymphocytes, monocytes and plasma cells are not included in the M:E ratio.

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Gaucher Cell

A Gaucher cell is a histiocyte (macrophage) whose cytoplasm is filled with linear or fibrillar material (kerasin). This cell is characteristic of the congenital glycolipid disorder, Gaucher's disease. Gaucher cells may also be seen in the marrow of patients with chronic granulocytic leukemia. When seen in this condition, they are referred to as pseudo-Gaucher cells.

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Evaluating M:E Ratio in a Patient with Chronic Lymphocytic Leukemia.

A thin area of a slide taken from a patient who has chronic lymphocytic leukemia, which is characterized by an increased number of small lymphocytes in the bone marrow. At this power, numerous small dark cells similar in appearance to immature red cells are seen, but can be quickly confirmed as lymphocytes when viewed under oil. The actual M:E ratio is normal, since lymphocytes are not included in the final ratio. The arrows show several cell most likely representing small lymphocytes. Some small lymphocytes are normal in the bone marrow.

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Bone marrow examination may be used to aid in the diagnosis of:View Page

Introduction to the ABO Blood Group System
ABO Antibodies and Aging

ABO antibodies are not usually produced by an infant until 3 to 6 months of age. Antibodies found in the sera of newborns are almost always IgG, passively acquired from the mother. Thus, serum testing of newborns is not performed. Anti-A and anti-B titers are highest at ages 5-10 years and then they gradually decrease. Thus, in elderly patients, ABO antibodies may be difficult to detect. In patients with hypogammaglobulinemia, some leukemias, lymphomas or patients who are taking immunosuppressive drugs, the expected antibodies may be weak or even absent, reflecting the low levels of gamma globulin in the patient’s serum. As previously mentioned, these and other ABO typing discrepancies must be resolved before true ABO type can be determined.

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Medical Error Prevention
Which occurrence is a medical error?View Page

Mycology: Hyaline and Dematiaceous Fungi
The fungus illustrated in this photomicrograph was recovered from an induced sputum specimen from a 74 year old man with chronic obstructive pulmonary disease. This isolate is most likely:View Page

Red Cell Morphology
Elliptocytes

Another example of elliptocytes as seen in hereditary elliptocytosis. Other conditions which may have varying numbers of elliptocytes include thalassemias, iron deficiency, megaloblastic anemia and anemia associated with leukemia.

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The Urine Microscopic: Microscopic Analysis of Urine Sediment
Uric Acid Crystal Morphology

The morphology of uric acid crystals varies more than any other type of crystal, from "whetstone" to hexagonal plate, from rosettes to rectangles or other irregular shapes. Their color also can vary from almost colorless to yellow or brown. Large numbers of uric acid crystals may be seen in individuals with leukemia or patients undergoing chemotherapy.

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Tuberculosis Awareness for Healthcare Workers
High Risk Progression Groups

The following persons are at high risk for progression from LTBI to TB disease: Persons infected with HIV Persons infected with Mycobacterium tuberculosis within the past two years Persons with untreated or inadequately treated TB disease Infants and children <4 years of age Persons with chronic medical conditions or immunocompromising conditions

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Variations in White Cell Morphology - Granulocytes
Auer rods are significant when they are seen in the cytoplasm of blast cells because they are diagnostic for:View Page
Auer Rods

Auer rods are red staining, needle-like bodies seen in the cytoplasm of myeloblasts, and/or progranulocytes in leukemia. Auer rods are cytoplasmic inclusions which result from an abnormal fusion of the primary (azurophilic) granules. Single or multiple Auer rods may be seen in the cytoplasm of a cell. If more than one is present, they are frequently close together and may even be overlapping. Their identification is very important because, if found, they can confirm the presence of myeloblasts indicating the presence of a myeloid (non-lymphoblastic) leukemia. They can also be seen in myeloid blast crisis in chronic granulocytic leukemia. Auer rods are never seen in lymphoblasts. This differentiation is important because the treatment of lymphoblastic and myeloblastic leukemia are different. Auer Rods always classified as pathological.

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More on Dohle Bodies

Dohle bodies are seen in a number of conditions, including infections, burns, measles, leukemia and chemotherapy. Dohle bodies are classified as pathological in the sense that they are only present when the body is responding to an unusually severe stress or stimulus. This severe stress may cause the cytoplasm of some cells to mature improperly. Their presence does not aid in the diagnosis of the disorders in which they are found, but they are frequently seen along with toxic granulation and/or vacuoles often present in infections and burns. Recognition is important because their appearance is similar to May-Hegglin bodies, which appear in a rare hereditary disorder called May-Hegglin anomaly.

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White Cell and Platelet Disorders: Peripheral Blood Clues to Nonneoplastic Conditions
The cells included in the composite image were found in a peripheral blood smear with a total WBC of 24,500/mm3. The differential count was: myelocytes 1 metamyelocytes 4 band neutrophils 15 segmented neutrophils 40 monocytes 8 eosinophils 2 basophils 1 lymphocytes 29. This hematologic picture is most consistent with:View Page
Normal Bone Marrow

Illustrated in the photograph is a normal bone marrow smear stained with Wright/Giemsa stain. Note the evenly distributed cells with normal maturation in both the myeloid and erythroid maturation sequences.An estimation of the percentage composition of cells can be made by experienced observers from scanning of multiple fields. In some instances a detailed differential count of 300 or more cells must be made.In normal bone marrows, the myeloid to erythroid ratio (M:E ratio)ranges from 1.2:1 to 5:1.A ratio of less than 1.2:1 indicates depressed leukopoiesis or erythroid hyperplasia. Ratios of 6:1 or greater usually indicates infection, erythroid hypoplasia, or chronic myelogenous leukemia.An assessment of the overall cellularity is also useful. In general, cellularity of less than 25% indicates hypoplasia; greater than 75% indicates hyperplasia.

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The upper photograph of this bone marrow section also reveals distinct hyperplasia with total replacement of the fat. The lower photograph is a Wright/Giemsa stain. Calculate the M:E ratio of the distribution of myeloid and erythroid cells in the lower photograph. The peripheral white blood count was 18,500/cumm. The most likely associated condition is:View Page
Assume that several other lymphocytes similar to the one in the center of the photograph are found on review of the peripheral smear. A work up for leukemia should be recommended.View Page
Additional comments on this exercise

The following pages in this presentation includes a series of white blood cell abnormalities that may be identified in a peripheral blood smear. Many of the cases will simulate the practice of a peripheral smear review by a hematology morphologist. He/she must asses what responses in patient care may be triggered by the clinician attempting to interpret the reported findings on a peripheral smearObservations of white blood cell abnormalities in the peripheral blood smear should be reported so as to direct the physician to an immediate specific diagnosis, such as: (1) atypical lymphocytes suggesting infectious mononucleosis rather than leukemia, (2) toxic granules in neutrophils as in acute infections, or atypical granules suggesting a genetic disorder, (3) an unusual mix of cells, such as too many or too few neutrophils, monocytes, or other myeloid cells, and (4) the presence of giant platelets, myelocytes, or other cells suggesting a myelodysplastic syndrome.In summary, laboratory data should be presented to clinicians in a user friendly way to promote effective decision making. The design of the data base of information must be directed toward providing clinically helpful information clearly and quickly in order to facilitate appropriate action in terms of optimizing patient care outcomes.d

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The neutrophils illustrated in this photograph are representative of those seen in the smear. The total WBC was 28,500 cells/cumm. The appropriate report to be issued following a morphology consultation would be:View Page
Typical cells on a peripheral blood smear as photographed here were repeatedly encountered as the smear was reviewed. The peripheral white blood cell count was 51,000/ml with an orderly maturation sequence. The comment "leukemoid reaction" may properly be appended to the report.View Page
A peripheral blood smear with many myeloid cells (photograph) was presented for morphology review. Toxic vacuoles in the neutrophil and monocyte most likely represent:View Page
The association of increased platelets accompanying neutrophilia and toxic granululation as illustrated in this photograph is called thrombocythemia.View Page
Leukemoid reaction revisited

The term leukemoid reaction is used to describe peripheral white blood cells that on the stained blood smear may have some resemblances to leukemia cells. Quantatively in a leukemoid reaction, the neutrophil count is >50,000 cumm with more immature cells, particularly myelocytes, than are usually present in toxic left shift syndromes. The presence of immature cells in a leukemoid reaction awakens thoughts of leukemia. Great care must be taken to make a distinct differentiation between aberrant white blood cell proliferations and a benign but exaggerated granulocytic proliferative response. Our material is from a 1-month-old girl with Down's syndrome. Her total white blood count was 37,000/mm3 interpreted as leukocytosis with left shift. Leukocytosis with a left shift, and leukemoid reactions with high alkaline phosphatase are conditions to be mindful of in patients with Down's syndrome. The alkaline phosphatase score is high in leukemoid reactions, low in granulocytic leukemia.

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Auer Rod

Illustrated in the photograph is a immature granulocyte with a distinct rod-shaped intracytoplasmic inclusion. This inclusion is known as an Auer rod, which is seen in up to 10% of blast cells in patients with acute myelogenous leukemia. An Auer red is the fusion of primary granules into rod-like inclusions.

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The cell illustrated in the photograph is known as a faggot cell.View Page
The cytoplasmic inclusion illustrated at the tip of the blue arrow is characteristic of:View Page
Doehle Bodies: Review

Doehle bodies are discrete, round or oval aggregates at the cytoplasmic periphery of neutrophils (blue arrows in figures). They stain sky blue with Romanowsky's stain and often may be deceivingly inconspicuous. In electron-micrographs, Doehle bodies are recognized as lamellar aggregates of rough endoplasmic reticulum. Although not considered a marker for leukemia, Goudsmit, et al (Brit J Hematol 20:447-562, 1971)reported their presence in family members, 2 sisters and 3 brothers. Two of the brothers died of acute myeloblastic leukemia. These testimonials indicate that Doehle bodies, when identified in peripheral blood smears, should be taken seriously so as to stimulate a clinical investigation of the patient.

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Eosinophilia Follow-Up

As mentioned on the previous page, high percentages of eosinophils may be present in the peripheral blood smears of patients with a variety of conditions--asthma, urticaria, Loeffler's syndrome, larval parasitic infections and in chronic eosinophilic leukemia. One exception to the association of eosinophilia with parasitic infections is a fatal case of disseminated strongyloidiasis reported many years ago by Miale (Hematology--5th Edition, Mosby, pg. 776, 1977) in which the peripheral blood eosinophilia was masked by the administration of corticosteroids.

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The peripheral blood smear presented here was submitted for morphological/clinical review. Conditions in which this picture may be seen include:View Page
Basophils

A basophil and a small lymphocyte are compared in the same field of the upper photograph, A single basophil is shown in the lower photograph.The cytoplasmic granules of the basophil are larger than the granules of toxic granulation.They contain chemical mediators of immediate hypersensitivity, and are found in the cytoplasm and overlying the nucleus (better seen in the lower photograph). Basophilic granules stain metachromatically with toluidine blue indicating the presence of acid mucopolysaccharide or proteoglycans, both thought to be heparin or heparin-like substances.Basophils are related to tissue mast cells, each involved in hypersensitivity responses and following anaphylactic episodes.Under the stimulation of complement components C3a and C5a, many mediators are released from the basophil granules, including histamine, heparin, and eosinophil chemotactic factors of anaphylaxis, or ECF-A.Basophils are the least common neutrophils in the peripheral blood, comprising 2% or less of the differential count.The presence of large granules of irregular size in basophils and the admixture of eosinophilic granules may indicate dysplastic changes associated with myelodysplastic disorders and leukemia.

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The cell photographed here is known as a MOTT cell. The condition in which these cells are associated is:View Page
The smudge cells pictured in the photograph may be found in each of the following situations except:View Page
The peripheral smear photographed here was submitted for morphologic/clinical examination.The predominant cells comprised 70% of the total white blood cells and are consistent with lymphocytes in a 4 month old infant.View Page
The large blue staining cells represented here in the photographs comprise 50% of the total white blood count.This picture is most consistent with:View Page
More about lymphocytes, their impostors and varied faces

In this photograph of blood cells from yet another submitted slide, we find cells resembling lymphoblasts with increased nuclear/cytoplasmic ratios and dense, finely meshed nuclear chromatin. In addition, note the extrusion of delicate strands of cytoplasm from the outer cell membranes (blue arrow). These are cells connoting hairy cell leukemia (HCL). Under scanning electron microscopy, the cytoplasmic extensions appear to be either slender microvilli or delicate pseudopods. The most helpful confirmatory finding is the detection of acid phosphatase isoenzymne 5 in the cytoplasm of suspected hairy cells by staining. The enzyme concentrates primarily in golgi bodies and in the nuclear membrane and its staining is not inhibited by the addition of tartrate. Stated in another way, hairy cells on the peripheral smears are detected by their staining positively for tartrate-resistant acid phosphatase. Be suspicious of HCL if marrow resists aspiration-a consequence of reticulin fibrosis of the marrow in HCL.

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