Hematology ppt flashcards Unit 3



Download 0.98 Mb.
Page2/2
Date05.06.2018
Size0.98 Mb.
1   2

Deficiencies of _________ or _________ is associated with hypersegmentation

Vitamin B12 or folic acid

Hypersegmentation can exist along with what other conditions?

Abnormal enlarged oval-shaped erythrocyte

Pseudohypersegmentation can be seen in (old/new) segmented neutrophils

Old

Define Pelger-Huet anomaly

Hyposegmentation of mature neutrophils

What is a reflection of abnormal nucleic acid metabolism?

Abnormal nuclear maturation

Despite the abnormal morphology of the described condition above, is the cell still functional?

Yes.

Abnormal nuclear maturation is considered to be a _________ anomaly

Benign

Pseudoanomaly may be caused by? (2 causes)

  1. drug induced

maturational arrest associated with acute infections

How can May-Hegglin anomaly can be characterized?

By the presence of Dohle body-like inclusions in neutrophils, eosinophils, and monocytes



What kind of conditions co-exist in May-Hegglin anomaly?

Abnormally large and poor granulated platelets, and thrombocytopenia

What is the percentage of patients who do not have symptoms of May-Hegglin Anomaly?

50%

Those who do show symptoms usually have______________

Abnormal bleeding tendencies

What is defined as a rare morphological abnormality of mature granulocytes that is considered a hereditary disease?

Chediak-Higashi syndrome

How is Chediak-Higashi syndrome characterized?

Very large granules that represend abnormal lysosomal development in neutrophils and other leukocytes

In Chediak-Higashi Syndrome, which WBC displays impaired chemotaxis and a delayed killing of ingested bacteria?

Neutrophils

Patients with Chediak-Higashi Syndrome suffer from frequent infections, which signify what?

That neutrophils are not efficient bacteriocidal cells

Alder-Reilly inclusions indicate what color particles?

Purple-red



What are these particles? And which cells are they mainly seen in?

Mucopolysaccharides seen mainly in neutrophils, eosinophils, basophils.

These particles are sometimes seen in which cells?

Monocytes and lymphocytes

Alder-Reilly granules resemble __________ ____________.

Toxic granulation

Alder-Reilly granules are mostly seen in what kind of patients?

Patients with Hurler, Hunter, and Maroteaux-Lamy types of genetic mucopolysaccharidosis.

True or False: Is Ehrlichia a morphological abnormality of mature granulocytes?

True

What is the correct technical name of Ehrlichia?

Human granulocytic ehrlichiosis (HGE) represents the second recognized.

When was ehrlichial infection of humans in the United States and was first described in?

1994

True or False: Does Ehlrichia represents the second most recognized human infection in the United States?

True

Give 2 examples of abnormal inclusions can be seen in granulocytes obtained from body fluids.

  1. Bacteria

Histoplasma capsulatum

Name 3 types of Qualitative Disorders.

  1. Defective locomotion and chemotaxis

  2. Defects in microbicidal activity

  • Monocyte-macrophage disorders

What is defective locomotion and chemotaxis?

  • A significant defect in the cellular response to chemotaxis

Defective locomotion and chemotaxis is commonly seen in patients who have __?


  • Diabetes mellitus
    Chédiak-Higashi anomaly

  • Sepsis

  • High levels of antibody IgE, (Job syndrome)

Define defects in microbicidal activity?


  • Neutrophils and monocytes possess oxidase systems capable of killing ingested microorganisms in the process of phagocytosis.

Defects in microbicidal activity disorders include ___?


  • CGD

  • Myeloperoxidase deficiency

  • Other functional anomalies of neutrophils.

Name 2 defects in microbicidal activity.


  1. Chronic granulomatous disease

  2. Myeloperoxidase deficiency



How many hereditary defects and additional disorders of neutrophil function have been described.

  • 15 and 30

True or False: Lactoferrin deficiency is a functional anomaly of neutrophils?

  • True

Give 2 examples of Monocyte-macrophage disorders.

  1. Gaucher disease

  • Niemann-Pick disease

What is Gaucher disease is caused by?

  • A disturbance in cellular lipid metabolism.

What is Neimann-Pick?

  • An inherited abnormality of lipid metabolism. Sphingomyelin accumulates in the tissue macrophages

What do Human granulocytic ehrlichiosis (HGE) represent?

the second recognized ehrlichial infection of humans in the United States and was first described in 1994

Where can certain abnormalities of mature granulocytes be found?

Certain abnormal inclusions can be seen in granulocytes obtained from body fluids

What are three qualitative disorders?

Defective locomotion and chemotaxis, microbicidal activity, monocyte-macrophage disorders

A significant defect in the cellular response to chemotaxis is seen in what kinds of patients?

diabetes mellitus, Chédiak-Higashi anomaly, and sepsis as well as in patients with high levels of antibody IgE, such as those with Job syndrome

Disorders due to defects in microbicide activity?

These disorders include CGD, myeloperoxidase deficiency, and other functional anomalies of neutrophils.

How many disorders of neutrophil function have been described?

At least 15 hereditary defects and 30 disorders

A functional anomaly of neutrophils includes what?

includes lactoferrin deficiency.

What are two monocyte-macrophage disorders?

Gaucher disease, Niemann-Pick disease

What is Gaucher disease is caused by?

a disturbance in cellular lipid metabolism

What is Niemann-Pick Disease?

an inherited abnormality of lipid metabolism. Sphingomyelin accumulates in the tissue macrophages.

The lymphocytes and plasma cells cooperate in defending the body against, what?

Diseases

How does the lymphocytes and plasma cells defending the body against disease?

Through recognition of foreign antigens and antibody production.

During embryonic development, Where does lymphocytes arise from the pluripotent, precursor cells?

Yolk sac and Liver

Later in fetal development and throughout the life cycle, Where is the sole provider of hematopoietic stem cells?

Bone marrow

Name the 2 Primary lymphoid tissues.

  1. Bone marrow

Thymus

Name the 3 locations of Secondary lymphoid tissues.

  1. Lymph nodes

  2. Spleen

  • Peyer patches in the intestine

What does proliferation of the T and B lymphocytes in the secondary or peripheral lymphoid tissues is primarily depend on?

  1. Antigenic stimulation

Name the following 4 regions The T lymphocytes or T cells are located in:


  1. Perifollicular and paracortical regions of the lymph node

  2. Medullary cords of the lymph nodes

  3. Periarteriolar regions of the spleen

  1. Thoracic duct of the circulatory system

What are the 4 site B lymphocytes, or B cells, multiply and populate?


  1. Follicular and medullary areas (germinal centers) of the lymph nodes

  2. Primary follicles and red pulp of the spleen

  3. Follicular regions of gut-associated lymphoid tissue (GALT)

  1. Medullary cords of the lymph nodes

What is the lifespan of a mature T lymphocyte?

  1. Several months or years

What is the average life span of the B lymphocytes?

  1. Few Days

What are the stages of lymphocyte development?


These are: lymphoblast, prolymphocyte, and mature lymphocyte.


How are general variations in lymphocyte morphology?


The term variant denotes that a lymphocyte is not normal but does not further classify a lymphocyte.

Healthy persons may have up to 5% or 6% of variant lymphocytes.



What are general characteristics of variant lymphocytes?

Usually, the overall size is increased (16 to 30 mm).

The nucleus may be enlarged.

The nuclear shape may be lobulated or resemble the nucleus of a monocyte (monocytoid) with clefts or notching and may be folded.

Chromatin patterns vary from fine patterns to a coarsely granular appearance.

One to three nucleoli may be present.

The cytoplasm is frequently abundant and often foamy or vacuolated.

Cytoplasmic color may range from gray to light blue or intensely blue.

Granules may be present



How many specific lymphocytes morphological vitiate?

Binucleated lymphocytes

Rieder cells

Vacuolated lymphocytes

Smudge cells




What are binucleated lymphocytes?

Binucleated lymphocytes are seen in viral infections. If more than 5% of the lymphocytes are binucleated, it suggestive of either lymphocytic leukemia or leukosarcoma.

What is rieder cell?

Rieder cells are similar to normal lymphocytes, except that the nucleus is notched, lobulated, and cloverleaf-like. They occur in chronic lymphocytic leukemia or can be artificially produced through blood smear preparation.

What are smudge cells?

Smudge cell is a natural artifact produced in the preparation of a blood smear.

How smudge cell represent?

Increased fragility of cells contributes to the increased percentage of smudge cells.

Some laboratories enumerate smudge cells as a percentage of the total 100 leukocytes in a differential leukocyte count.

Smudge cells are seen in increased proportions in lymphocytosis, particularly chronic lymphocytic leukemia.


What are vacuolated lymphocytes?


They are frequently associated with Niemann-Pick disease, Tay-Sachs disease, Hurler syndrome, and Burkitt lymphoma. Vacuoles can also be seen in variant lymphocytes and as a reaction to viral infections, radiation, and chemotherapy

How many major lymphocyte categories and functions are recognized?


These categories are: T cells, B cells, and natural killer (NK) lymphocytes.

What are T cells responsible for?

T cells are responsible for cellular immune responses and are involved in the regulation of antibody reactions by either helping or suppressing the activation of B lymphocyte.

Sensitized T lymphocytes protect humans against infection by mediating intracellular pathogens that are viral, bacterial, fungal, or protozoan.

These cells are responsible for chronic rejection in organ transplantation


How is about B lymphocyte responsed?

B cells serve as the primary source of cells responsible for humoral (antibody) responses.


How natural killer lymphocytes are recognized?

These are recognized as a unique and important part of the immune system with roles in infectious disease and tumor surveillance.

NK cells, derived from CD34+ hematopoietic progenitor cells, belong to the innate immune system. Unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration



What are functions of monoclonal antibodies?


Monoclonal antibodies to cell surface antigens now provide a method of classifying and identifying specific cellular membrane characteristics

What is identified with a monoclonal antibody?


The naming of the surface membrane antigen is identified with a monoclonal antibody.


What are functions of T cells?

CD4 T cells play a central role in immunity. The functions of CD4 T cells include the following:

Helping B lymphocytes make antibodies

Inducing macrophages to develop enhanced microbicidal activity

Recruiting neutrophils, eosinophils, and basophils to sites of inflammation or infection



Producing cytokines and chemokines to integrate immune responses


What's the early pre-B cell?

The early pre-B cell is terminal deoxynucleotidyl transferase (TDT)-positive and expresses HLA-DR, CD19, and usually common ALL antigen (CALLA [CD10]) antigen.

Whats the immunoglobulin unique characteristic of the pre-B cells?

  • The first unique feature that identifies pre-B cells is the appearance of immunoglobulin chains in the cytoplasm.

  • Immunoglobulins consist of light and heavy molecular weight chains. The heavy chain (m) of IgM is synthesized first and characterizes the pre-B cell.

  • Other markers include TDT, CD19, CD20, CALLA, and HLA-DR.

In the next stage of maturation, the early or immature B cell has cytoplasmic (cIg) and surface immunoglobulin (sIg) in the form of complete heavy and light chain molecules of IgM.

What's the functional testing of lymphocyte cells?

  • Functional testing of lymphocytes

  1. Tests of T lymphocyte function measure mediator production. Soluble mediators (cytokines) are secreted by monocytes, lymphocytes, or neutrophils, providing the language for cell-to-cell communication.

What are the funtions and membrance characteristics of lymphocytes?

  • Important cytokines are as follows:

  • Migration inhibition factor (MIF): affects macrophage migration during delayed hypersensitivity reactions

  • IL-2 (T cell growth factor): major factor stimulating T-cell proliferation

  • Chemotactic factor: attracts granulocytes to affected areas

  • IL-1: released by macrophages and activates helper T cells

What are the Plasma cell development and Maturation morphology?

  • Maturational morphology

  • Mature B Cell (after blast transformation)

  • Plasmacytoid Lymphocytes

  • Plasma cell

What are the physical characteristic of th mature B cell after blast transformation?

  • The overall size is 8 to 20 mm.

  • The nucleus may be round or oval and may be eccentrically placed (not in the middle of the cell).

  • The chromatin may be arranged in a fine pattern.

  • The cytoplasm is nongranular, is moderate in amount, and has a mottled blue color.

What are the physical characteristics of plasmacytoid lymphocytes?

  • The overall size is 15 to 25 mm.

  • The round or oval nucleus is eccentrically placed.

  • The chromatin is coarse and irregularly spaced.

  • Nucleoli may be visible.

  • Usually, the cytoplasm is distinctive dark blue with a lighter-staining area, the hof, next to the nucleus. The hof represents the area containing the Golgi apparatus.

Where are the plasma cells found and their physical characteristics?

  • The mature plasma cell is not normally found in peripheral blood.

  • About 1% or 2% of plasma cell−like lymphocytes may be encountered under stress conditions.

  • The overall cell size is 14 to 20 mm.

  • The nucleus is small and eccentrically located. More than one nucleus may be seen in a cell. The chromatin is condensed and has a cartwheel configuration.

  • Although the cytoplasm is dark blue, the hof area is usually visible. The cell has a well-developed, rough endoplasmic reticulum, which is characteristic of a cell producing proteins for export. The distinctive dark-blue cytoplasm is indicative of active synthesis and secretion of proteins (antibodies).

What are the characteristics of the Flame Cell?

  • Cytoplasm stains a bright-red color and contains increased quantities of glycogen or intracellular deposits of amorphous matter.

Where are the plasma cells disorder found?

  • Not normally found in the peripheral blood

  • In plasma cell dyscrasias, the plasma cells may be greatly increased or may completely infiltrate the bone marrow, for example, Waldenström macroglobulinemia and multiple myeloma.

What are the physical characteristics of Lymphocytes?

  • The normal range for lymphocytes in an adult is 22% to 40%, with absolute values of 1.1 to 4.4 x 109/L.

  • Absolute number = total leukocyte count × relative % of lymphocytes

A value less than the normal reference range is called lymphocytopenia. When the blood lymphocyte count increases above the upper limit of the reference range, the condition is referred to as lymphocytosis.

Where are lyphocytosis normally found?

  • Lymphocytosis is natural and normal in infants and children up to approximately 10 years old, with total lymphocyte counts as high as 9 x 109/L. This increase probably results from the limited production of adrenal corticosteroid hormones during this period of the life cycle. This limited production of hormones may underlie the lymphocytosis seen in later childhood in conditions such as malnutrition and scurvy.

  1. Lymphocytosis is not a common nonspecific response to inflammation as is neutrophilia.

In adults, how are lymphocytosis change?

  • In adolescence and adulthood, nonmalignant conditions associated with an absolute lymphocytosis include the following:

  • Acute viral infections (e.g., infectious mononucleosis, infectious hepatitis, posttransfusion syndrome, CMV infection, and infectious lymphocytosis)

  • Some bacterial infections (e.g., Bordetella pertussis infection [whooping cough] and brucellosis)

  • Parasitic infections (e.g., toxoplasmosis)

  • Drug reactions (e.g., p-aminosalicylic acid hypersensitivity and phenytoin hypersensitivity)

  1. Uncommon causes (e.g., tertiary and congenital syphilis and smallpox)

What are the malignant conditions that produce lymphocytosis?

  • Malignant conditions that produce lymphocytosis:

  • Lymphocytic leukemia (acute and chronic forms)

  • The leukemic phase of lymphomas

  • Waldenström macroglobulinemia

  • Cancer

What the the disorders associated with lymphocytosis?

  • Infectious mononucleosis

  • Cytomegalovirus infection

  • Toxoplasmosis

  • Infectious lymphocytosis

  1. Bordetella pertussis (Haemophilus pertussis) infection

What is the infectious Mononucleosis?
What is EBV?

  • Infectious mononucleosis is usually an acute, benign, and self-limiting lymphoproliferative condition caused by Epstein-Barr virus (EBV).

  • EBV is also the cause of Burkitt lymphoma, a malignant tumor of the lymphoid tissue occurring mainly in African children; nasopharyngeal carcinoma; and neoplasms of the thymus, parotid gland, and supraglottic larynx.

What are the laboratory testing necessary to esablish or confirm a diagnosis of infectious mononucleosis?

  • Laboratory testing is necessary to establish or confirm a diagnosis of infectious mononucleosis.

  • Hematological studies reveal leukocyte counts ranging from 10 to 20 × 109/L in approximately two thirds of patients; about 10% of the patients with this disorder demonstrate leukopenia.

  1. A differential leukocyte count may initially disclose neutrophilia, although mononuclear cells usually predominate as the disorder develops. Typical relative lymphocyte counts range from 60% to 90%, with 5% to 30% variant lymphocytes. These variant lymphocytes exhibit diverse morphological features and persist for 1 to 2 months in some patients and as long as 4 to 6 months in others.

What are the laboratory tests for infectious mononucleous?

  • If the classic signs and symptoms of infectious mononucleosis are absent, a diagnosis of infectious mononucleosis is more difficult to make.

  • The diagnosis may be established by antibody testing. The antibodies present in patients with infectious mononucleosis are heterophil and EBV antibodies. Rapid slide tests that use the principle of agglutination of horse erythrocytes are available. The use of horse erythrocytes appears to increase the sensitivity of the test.

What is Cytomegalovirus Infection?

  • Human CMV is classified as a member of the herpes family of viruses. There are currently five recognized human herpes viruses: herpes simplex I, herpes simplex II, varicella-zoster virus, EBV, and CMV.

  • In patients with CMV infection, hematological examination of the blood usually reveals a characteristic leukocytosis. A slight lymphocytosis with more than 20% variant lymphocytes is common. Clinical chemistry assays may demonstrate abnormal liver function. Another assessment of the presence of infection is the demonstration of inclusion bodies in leukocytes in urinary sediment.

  • A definitive diagnosis can only be made by isolating the virus from urine or blood samples or by demonstrating CMV-specific IgM or increasing CMV-specific IgG antibody titers.

What is the normal range of lymphocytes with absolute values?

The normal range for lymphocytes in an adult is 22% to 40%, with absolute values of 1.1 to 4.4 x 109/L.

How is the absolute number of leukocyte calculated?

Absolute number = total leukocyte count × relative % of lymphocytes

What are the terms referring to low and high number of lymphocytes in the blood?

A value less than the normal reference range is called lymphocytopenia. When the blood lymphocyte count increases above the upper limit of the reference range, the condition is referred to as lymphocytosis

How is the number of lymphocytes change in children; and to what conditions lymphocytosis may relate?

Lymphocytosis is natural and normal in infants and children up to approximately 10 years old, with total lymphocyte counts as high as 9 x 109/L. This increase probably results from the limited production of adrenal corticosteroid hormones during this period of the life cycle. This limited production of hormones may underlie the lymphocytosis seen in later childhood in conditions such as malnutrition and scurvy.

Which is a more common non-specific response to inflammation? Lymphocytosis or neutrophilia?

Lymphocytosis is not as common of a nonspecific response to inflammation as is neutrophilia.

What are the nonmalignant conditions associated with lymphocytosis in both adolescence and adulthood?

In adolescence and adulthood, nonmalignant conditions associated with an absolute lymphocytosis include the following:

Acute viral infections (e.g., infectious mononucleosis, infectious hepatitis, posttransfusion syndrome, CMV infection, and infectious lymphocytosis)

Some bacterial infections (e.g., Bordetella pertussis infection [whooping cough] and brucellosis)

Parasitic infections (e.g., toxoplasmosis)

Drug reactions (e.g., p-aminosalicylic acid hypersensitivity and phenytoin hypersensitivity)

Uncommon causes (e.g., tertiary and congenital syphilis and smallpox)



What are the malignant conditions which produce lymphocytosis?

Malignant conditions that produce lymphocytosis:

Lymphocytic leukemia (acute and chronic forms)

The leukemic phase of lymphomas

Waldenström macroglobulinemia

Cancer


What disorders are associated with lymphocytosis?

Infectious mononucleosis

Cytomegalovirus infection

Toxoplasmosis

Infectious lymphocytosis



Bordetella pertussis (Haemophilus pertussis) infection

What is infectious mononucleosis and what causes it?

Infectious mononucleosis is usually an acute, benign, and self-limiting lymphoproliferative condition caused by Epstein-Barr virus (EBV).

What other conditions does EBV cause in which ethnic group?

EBV is also the cause of Burkitt lymphoma, a malignant tumor of the lymphoid tissue occurring mainly in African children; nasopharyngeal carcinoma; and neoplasms of the thymus, parotid gland, and supraglottic larynx.

Which age group is infectious mononucleosis the most frequent suggested by three studies?



What diagnostic method is necessary to establish infectious mononucleosis?

Laboratory testing is necessary to establish or confirm a diagnosis of infectious mononucleosis.

What are the leukocyte counts in what percent of patients with infectious mononucleosis?

Hematological studies reveal leukocyte counts ranging from 10 to 20 × 109/L in approximately two thirds of patients; about 10% of the patients with this disorder demonstrate leukopenia.

How are the leukocyte counts change with morphological diversity during the development of infectious mononucleosis?

A differential leukocyte count may initially disclose neutrophilia, although mononuclear cells usually predominate as the disorder develops. Typical relative lymphocyte counts range from 60% to 90%, with 5% to 30% variant lymphocytes. These variant lymphocytes exhibit diverse morphological features and persist for 1 to 2 months in some patients and as long as 4 to 6 months in others.

What is a characteristic of infectious mononucleosis under the microscope?



What happens if the classic signs and symptoms are absent in infectious mononucleosis?

If the classic signs and symptoms of infectious mononucleosis are absent, a diagnosis of infectious mononucleosis is more difficult to make.

What other laboratory methods can be used to establish the diagnosis?

The diagnosis may be established by antibody testing. The antibodies present in patients with infectious mononucleosis are heterophil and EBV antibodies. Rapid slide tests that use the principle of agglutination of horse erythrocytes are available. The use of horse erythrocytes appears to increase the sensitivity of the test.

What is the order of antibody response to infectious mononucleosis?



How is the human cytomegalovirus is classified?

Human CMV is classified as a member of the herpes family of viruses. There are currently five recognized human herpes viruses: herpes simplex I, herpes simplex II, varicella-zoster virus, EBV, and CMV.

What are the laboratory results which indicate a CMV infection?

In patients with CMV infection, hematological examination of the blood usually reveals a characteristic leukocytosis. A slight lymphocytosis with more than 20% variant lymphocytes is common. Clinical chemistry assays may demonstrate abnormal liver function. Another assessment of the presence of infection is the demonstration of inclusion bodies in leukocytes in urinary sediment.

How a definitive diagnosis can be made?

A definitive diagnosis can only be made by isolating the virus from urine or blood samples or by demonstrating CMV-specific IgM or increasing CMV-specific IgG antibody titers.

What is the organism which causes toxoplasmosis?

The microorganism Toxoplasma gondii causes toxoplasmosis. Toxoplasma gondii was recently recognized as a tissue Coccidia.

How does toxoplasmosis resemble infectious mononucleosis?

Both clinical and laboratory findings in this disease resemble infectious mononucleosis.

What is a typical sign of toxoplasmosis which can be seen on a blood smear?

An increased number of variant lymphocytes can be seen on a peripheral blood smear.

How is the definite diagnosis established?

The diagnosis is established by serologically demonstrating significant elevations of Toxoplasma antibodies.

What is the leukocyte count in infectious lymphocytosis?

Leukocytosis with lymphocytosis characterizes this disease. It may precede clinical manifestations of the disease with leukocyte counts of 20 to 50 × 109/L.

What do the differential peripheral blood counts show in infectious lymphocytosis?

Differential peripheral blood counts reveal up to 95% small, mature, normal-appearing lymphocytes. These lymphocytes are probably of T-cell origin. No lymphoblasts are present. An increase in eosinophils may be noted.

Which tests are negative in infectious lymphocytosis?

Results of heterophil and EBV antibody tests are negative.

What are the leukocyte counts of children with chronic infectious lymphocytosis?

In children with the chronic form of infectious lymphocytosis, the leukocyte count ranges from 10 to 25 × 109/L, with a predominance of normal-appearing lymphocytes. Other leukocytic alterations are minimal.

What is the organism which causes whooping cough?

Whooping cough is caused by B. pertussis, a bacterial organism that produces inflammation of the entire respiratory tract.

What are total leukocyte and lymphocyte counts in whooping cough?

The total leukocyte count can be increased to as high as 100 × 109/L, with an absolute lymphocyte value of as high as 50 × 109/L. The absolute lymphocyte value is usually 15 to 40 × 109/L. These leukocyte and lymphocyte values are major laboratory findings and may be present if the characteristic cough has not yet developed or is mild enough to be missed during physical examination.

What does the peripheral blood smear show in whooping cough?

On a peripheral blood smear, the lymphocytes are small and mature, with only a rare occurrence of lymphoblasts. A definitive diagnosis can be made on isolation of the bacteria.

How is lymphocytopenia defined?

Lymphocytopenia is generally defined as less than 3.0 × 109/L lymphocytes in adults or less than 1.5 × 109/L lymphocytes in children.

How are the immune disorders associated with lymphocytopenia classified?

Immune disorders may be caused by defects in the numbers or functional properties of lymphocytes and may be congenital or acquired. These conditions are usually classified as either T-cell or B-cell disorders. Some of the less common disorders involve both T and B cells.

What is DiGeorge syndrome and what do patients with this disorder exhibit?

A number of T-cell and B-cell defects involve the alteration of some lymphocyte subpopulations. Patients with DiGeorge syndrome exhibit a decrease in total T lymphocytes coupled with an increased ratio of helper to suppressor cells.

What is observed regarding the CD4-CD8 ratio on AIDS?

In AIDS, a reversed phenotypic CD4-to-CD8 ratio due to a decrease in helper cells is observed.

What are the signs of systemic lupus erythematosus?

A decrease in total T cells and a lack of, or reduced, suppressor cell population are among the immunological changes observed in active systemic lupus erythematosus.

Who was the first to recognize leukemia as a distinct clinical disorder between 1839-1845?

Virchow

Why did Virchow name the disorder leukemia?

because of the white appearance of the blood from patients with fever, weakness, and lymphadenopathy

What category are leukemias, lymphomas, myelomas?

proliferative diseases (neoplasms)

What and where is leukemia?

it is a disease of leukocytes in the blood and bone marrow

What is lymphoma?

a general term for malignancy that starts in the lymph system, mainly the lymph nodes

What are the two main types of lymphoma?

Hodgkin’s and non-Hodgkin’s

What is myeloma?

a form of cancer in the plasma cells where the cells overgrow forming a tumor

What does total leukocyte count determine?

whether a leukemia is acute or chronic

What characteristics do acute leukemias have?

symptoms of short duration, many immature cells forms in the bone marrow and/or peripheral blood, elevated total leukocyte count

What characteristics do chronic leukemias have?

symptoms of long duration, mostly mature cell forms in the bone marrow and/or peripheral blood, and total leukocyte counts that range from extremely elevated to lower than normal

What are the differences in the prognoses of survival in untreated acute forms and chronic forms?

several weeks to several months in acute forms and months to many years in chronic forms

What system has been enhanced with molecular information?

World Health Organization system

What is another form of leukemia classification?

French-American-British (FAB) classification

What are the three types of broad leukemias using the FAB system?

myelogenous, monocytic, lymphocytic

What are the three lineages for neoplasms according to the WHO system?

myeloid, lymphoid, histiocytic/dendritic cell

What are classifications based on?

morphology combined with immunophenotyping and genetic studies of peripheral blood, bone marrow, and lymph node samples

What is the significance of modern drugs on leukemias and the patients?

They are more effective against malignant cells and are less toxic to the patient, have a significant impact on the longevity of patients with many forms of leukemia and lymphoma

How does leukemia develop?

Subsequent to the malignant transformation of one or more normal hematopoietic progenitor cells

What are some factors that cause leukemias and lymphomas?

Genetic/immunologic factors, occupational/environmental exposure, chemical exposure, drug exposure, viral agents, etc.

What are the most common types of DNA changes that can lead to leukemia?

translocation

What occurs when part of a chromosome is lost?

deletions

When do inversions occur?

When part of a chromosome gets turned around/reversed

When do additions occur?

When an extra chromosome or part of one is gained.;

When and how is a single oncogene produced?

Through mutation in a target cell that is not sufficient to convert these cells into full-blown cancer cells

What are some examples of how cancer-predisposing genes may act?

they may alter the immune system’s ability to recognize and wipe out incipient tumors, they may affect a host’s ability to repair resulting damage to DNA, etc

What are proto-oncogenes?

central regulators of growth in normal cells and are antecedents of oncogenes

What are tumor suppressing genes?

Also known as antioncogenes; regulators of the proliferation of cell growth in normal cells

What are some examples of diffusible factors?

beta-interferon, tumor growth factor, tumor necrosis factor

What is an occupational factor associated with an increased incidence of leukemia?

ionizing radiation

Chemical exposure is more strongly linked to an increased risk of which leukemia?

Acute myelogenous leukemia

What is the most common translocation in ALL adults?

The Philadelphia chromosome, a swapping of DNA between chromosomes 4 and 11 aka., t(4;11) or 8 and 14 aka., t(8;14)

What virus has been linked to ALL?

The Epstein-Barr virus (EBV)?

When does secondary AML develop?

with a hematologic disorder, with an inherited disease, with myelodysplastic syndrome for at least three months, in those who have been treated with leukemogenic agents

Where are leukemias highest and lowest incidences?

highest in Scandinavian countries and Israel, lowest in Japan and Chile

At what ages are leukemias highest incidences, and death rates?

highest incidence among children aged 1-4, highest death rate among children aged 15-19

Which leukemia is slightly more common in boys than girls?

ALL

What is the male to female ratio in adults for CLL?

2:1

What is the WHO synonym for FAB M6A and M6B?

The WHO synonym is acute erythroid leukemia.

What is the median age seen suffering from Erythroleukemia?

The median age of occurrence is 54 years.

Is Erythroleukemia more prone in male or females?

It is more prone for males, having a 1.4:1 male:female ratio.

What is the average length of survival of someone having Erythroleukemia?

The average length of survival is 11 months.


What is the most common cancer encountered in children younger than 15?

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, representing 23% of cancer diagnoses among children younger than 15 years of age.

Does acute lymphoblastic leukemia only affect children?

No, ALL has a bimodal age distribution, peaking in children between 3 and 5 years of age and again in persons older than 65 years.

Does ALL affect males more than females? Is it more prominent in white or black children?

Pediatric ALL occurs slightly more often in boys than in girls and in white children more often than in black children.

What are the statistics for children to live with ALL for 5 years? 10 years?

About 85% of children with ALL live for 5 years or more, and 78.1% for 10 years.

Do adults have the same capability as children when being diagnosed for ALL?

Treatment of adults with ALL has lagged behind the results of treatment achieved with children.

What are the different classifications for ALL?

Acute lymphoblastic leukemia (ALL) is divided into the following:

-FAB L1 (children)

-FAB L2 (older children and adults)

-FAB L3 (patients with leukemia secondary to Burkitt lymphoma)



What biomarkers can be used to help in differentiating for ALL?

Surface markers, proteins on the cell membrane that can be detected with immunologic reagents, are extremely helpful in differentiating ALL.

Proteins expressed on the cell membrane help aid in the differentiation of what?

Different proteins are expressed at different stages of maturation, which allows them to be used as markers of both cell lineage and maturation.

What common antigen is found of the surface of lymphoblasts? What does CD20 indicate?

The common ALL antigen (cALLA) is found on the surface of lymphoblasts in 70% of patients with ALL. CD20 expression is associated with inferior survival in adults with ALL.

What is mixed lineage leukemia (MLL) and is it the same as ALL?

Mixed lineage leukemia (MLL) has been established to be a distinct disease and not a subtype of the prevalent acute lymphoblastic leukemias (ALL).

What DNA-based evidence do they have in order to differentiate MLL from ALL?

Using DNA microarray technology, gene profiles of more than 12,000 genes established that about 1,000 genes were underexpressed and about 200 were expressed at higher levels in MLL when compared to ALL. This gene expression signature distinguishes MLL from classic ALL.

Why are cytogenetic studies crucial for the correct diagnosis of AML or ALL?

Cytogenetic studies are important because two thirds of patients diagnosed with AML or ALL and 90% of patients with secondary leukemia will have leukemic blasts showing clonal chromosomal abnormalities. Chromosomal abnormalities differ between AML and ALL and among the various subtypes.

What gene should be studied in order to diagnose ALL or CML?

The BCR/abl, t(9;22) translocation qualitative assay by RT-PCR should be ordered to screen patients suspected of ALL or CML for the presence of the bcr/abl transcript.

What is a common characteristic within half of all patients with ALL?

About half of patients with lymphoblastic leukemia have abnormal karyotypes.

What chromosomal changes are seen within patients with ALL?

Gains in chromosome 21 and losses in chromosome 7, 9, or 20 have all been cited.

What are some cytochemical stains?

Sudan black B, Myeloperoxidase, Periodic acid–Schiff (PAS), Naphthol AS-D chloroacetate (NASDCA) esterase, Alpha-naphthyl acetate-butyrate esterase with fluoride inhibition, Leukocyte alkaline phosphatase (LAP), and Acid phosphatase with or without tartaric acid inhibition

How do the Sudan stains affect the cell?

The Sudan stains, such as Sudan black B, are substances belonging to a series of lipid-soluble pigments that detect cellular lipids.

Why are Sudan stains useful in diagnosing leukemias?

This procedure is helpful in differentiating acute myeloid leukemia from ALL.

Where is peroxidase found in the human body?

In humans, peroxidases are found in the microbodies of liver and kidney cells and in the granules of myeloid and monocytoid cells.

Is myeloperoxidase only located in primary, azurophilic granules?

No, primitive blasts that are committed to the myeloid cell line demonstrate myeloperoxidase activity in areas such as the endoplasmic reticulum and the Golgi region.

What does the Periodic acid-Schiff measure? Should neurophils have a large amount of the measured substance?

The periodic acid–Schiff (PAS) reaction is important in carbohydrate histochemistry. Positive staining reactions indicate the presence of glycogen, a polymer of glucose, and other 1,2-glycol–containing carbohydrates. Mature neutrophils contain high levels of cytoplasmic glycogen, which is physiologically related to the high energy needs of neutrophils in phagocytosis.

Which cells of immunity does PAS not target?

The PAS reaction is strongly positive in neutrophilic granulocytes except blast forms, immature and mature platelets, and erythrocytes in erythroleukemia (FAB M6).

Why is the PAS test clinically helpful?

The usefulness of this procedure is in establishing the negative characteristics of myeloblastic and monoblastic leukemias from lymphoblastic leukemias.

Which non specific esterase enzymes are used to recognize monocytic cells?

The nonspecific esterase enzymes alpha-naphthyl acetate and butyrate esterase are used clinically to recognize cells of monocytic origin. If the enzyme is of monocytic origin, it is inhibited by sodium fluoride.

What do alkaline phosphatases do?

Alkaline phosphataseChapter 26 contains a discussion of this cytochemical staining procedure and its clinical applications in distinguishing between leukemia and a leukemoid reaction.

How do acid phosphatases affect monocytes and lymphocytes?

Acid phosphatase monocytes demonstrate a more intense positive reaction than do neutrophils. Although lymphocytes display little activity, T cells do exhibit intense positivity in the Golgi region, whereas B cells may be positive or negative.

What diagnosis can immunophenotyping by flow cytometry confirm or establish?

Leukemia

Monoclonal antibodies play an important role in supplementary differential testing of what various ailments?

Leukemias and lymphomas

TdT, CD9, and CD79a positive in early B-cell precursors, hematogones are expressed by?

Precursor B cells

What is more frequently present in precursor B cell ALL, CD79 or CD 20?

CD79

Which CD marker is positive in the majority of cases of precursor B-cell ALL and is rare in T-cell ALL?

CD10

What two things are usually negative in mature B-cell ALL

TdT and CD99

What CD markers are unique to granulocytes and monocytes.

CD11b, CD11c, CD13, and CD14

What are some of the most common life-threatening emergencies confronting patients with acute leukemia

Infection, bleeding, leukemic infiltration of organs, metabolic abnormalities, hyperleukocytosis

In what phase of leukemia is chemotherapy done?

Introduction phase

Is stem cell transplant a viable treatment option for leukemia patients?

Yes

What is produced in large amounts by cells of MDS, AML, and CML patients?

Proteins

What are the peptides used in cancer vaccines combined with to make the vaccine?

Montanide

What are the cancer vaccines given with?

GM-CSF (sargramostim)

What is the purpose of giving Montanide and sargramostim?

They help the immune system respond to the vaccines

How do the cancer vaccines work?

They activate the immune system to make specialized cells that search out and kill the MDS, AML, and CML cells containing the two proteins.

What is the epidemiology of acute leukemias?

- There were an estimated 44,790 new cases of leukemia and an estimated 21,870 deaths from leukemia in the United States in 2009.

- As a group, the acute leukemias are characterized by the presence of blasts and immature leukocytes in the peripheral blood and bone marrow.



What is the relationship between anemia and acute leukemia?

- Anemia is usually present. Anemia can be caused by bleeding and the replacement of normal marrow elements by leukemic blasts.

- Although the total leukocyte count is usually elevated, some patients may demonstrate normal or decreased leukocyte counts.

- Thrombocytopenia is also usually present in patients with acute leukemia.


What is the prognosis of acute leukemia?

- Modern treatment methods have produced a high rate of survival in children. Significant progress has been made in the treatment of childhood acute leukemia.

- Treatment for chronic myelogenous leukemia and chronic lymphocytic leukemia has achieved impressive results in adults.

- The best time to achieve the longest remission and possible cure of acute leukemia via maximum cell kill is when the disease is first diagnosed.


What is the French-American-British (FAB) Categories of acute leukemia?

  • FAB classifications divide acute leukemias into two major divisions:

    • Acute myeloid leukemias (AMLs)

    • Acute lymphoblastic leukemias (ALLs)

  • The system groups

    • Acute myeloid leukemias into nine subtypes (M0 through M7)

ALL into three categories (L1 through L3)

How does the World Health Organization (WHO) Categorize acute leukemia?

- The underlying rationale behind the WHO classification is based on defining disease entities according to the biology of the disease, increasing the emphasis on underlying common genetic characteristics as well as clinical signs and symptoms.

- WHO classifications require the additional evaluation of the leukemic blasts by molecular analysis and flow cytometry.



  1. - WHO classification of AML incorporates and interrelates cellular morphology, cytogenetics, molecular genetics, and immunological markers to structure a classification system that is universally applicable and prognostically relevant.

What are the general characteristics of Acute Myeloid Leukemias?

- AML is the most common leukemia subtype.

- AML is a genetically heterogeneous clonal disorder characterized by a maturation block and the accumulation of acquired somatic genetic alterations in hematopoietic progenitor cells that alter normal mechanisms of self-renewal, proliferation, and differentiation.

- Classification of AML subtypes is clinically relevant because particular abnormalities are associated with distinct clinical behavior¾prognosis is favorable or unfavorable response to treatment.


What is the genetic difference of Acute Myeloid Leukemia (AML)?

There are two different subgroup for AML with genetic differences with disruption with:

- FLT 3 gene that encodes a type III receptor tyrosine kinase. FLT3 is known to be mutated in up to 30% of patients with AML.

- Core binding factor (CBF) complex, a transcription factor complex critical for regulation of hematopoiesis and normal myeloid development.

These two major subgroups of genetic disruptions in AML can demonstrate interaction in initiating and maintaining the leukemic clone.



What is the role of micro-RNA with AML?

- Micro-RNA expression is associated with cytogenetics, molecular and morphological alterations, and clinical outcomes in AML.

- Micro-RNAs are naturally occurring 19- to 25-nucleotide RNAs cleaved from 70 to 100 nucleotide precursors that hybridize to complementary mRNA targets and either lead to their degradation or inhibit their translation of the corresponding proteins.



What is AML?

Acute Myeloid Leukemia (AML) is characterized by an increase in the number of immature cells in the bone and arrest in their maturation

What is Acute Myeloid Leukemia (FAB M0)?

The subtype M0 consists of undifferentiated myeloid blasts.

What is Acute Myeloid Leukemia (FAB M1)?

- The WHO synonym for this condition is acute myeloblastic leukemia without maturation.

- This form of leukemia is the most common type of leukemia in children younger than 18 months of age, but it typically occurs in middle-aged adults with a median age of 46 years.

- The typical male:female ratio of FAB M1 is 1:1.

- The median survival time is 3.5 months after diagnosis.



What is Acute Myeloid Leukemia (FAB M2)?

- The WHO synonym for this disease is acute myeloblastic leukemia with maturation.

- Myeloblasts predominate on peripheral blood smears. The FAB M2 form of leukemia typically occurs in middle-aged persons.

- The median age of occurrence is 48 years; however, approximately 40% of cases occur in individuals of age 60 years or older.

- The approximate male:female ratio is 1.6:1.

The median survival time is 8.5 months.


What is Acute Promyelocytic Leukemia (FAB M3)?

- Laboratory findings may be similar to those of the FAB M2 type.

- In acute promyelocytic leukemia, the median age of occurrence is 38 years, with a median survival of approximately 16 months.

- The approximate male:female ratio is 2:1.

- Anemia and thrombocytopenia are present in most cases. Total leukocyte counts range from conditions of leukopenia to leukocytosis. Leukopenia is seen frequently. Promyelocytes are the predominating cell type.



Acute Myelomonocytic Leukemia
(FAB M4)

- Occurrence of this form of leukemia is uncommon in children and young adults.

- The highest frequency of occurrence is in adults older than 50 years of age.

- The average male:female ratio is 1.4:1.

Most forms of myelomonocytic leukemia are of the acute form, with the average length of survival being approximately 8 months.

- In FAB M4, proliferation of granulocytes and monocytes is characteristic.

Anemia and thrombocytopenia are present.



Acute Monocytic Leukemia (FAB M5)

- Pure monocytic leukemia is uncommon and constitutes less than 15% of all leukemias. Two forms exist: FAB M5A and FAB M5B.

- FAB M5A form is most common in young adults (median age, 16 years); the FAB M5B form has a peak occurrence characteristically during middle age (median age, 49 years).

- Male:female ratio is about 0.7:1 in the M5A form; the male:female ratio is approximately 1.8:1 in the M5B form.

- This form of acute leukemia is very resistant to therapy; the life expectancy is short, ranging from 5 to 8 months depending on the type.



What is the WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues?

fourth edition, has enhanced the classification of lymphoid neoplasms by including immunophenotypic features and genetic abnormalities to define different disorders.

How are Chronic leukemias generally characterized

by the presence of leukocytosis with an increased number of mature lymphocytes, lymphocytosis, on a peripheral blood film.


How are Malignant lymphoproliferative disorders are characterized?

by an accumulation of lymphocytes.

What are Both CLL and SLL are neoplasms composed of?

small B lymphocytes in the peripheral blood, bone marrow, spleen, and lymph nodes, mixed with prolymphocytes and paraimmunoblasts forming proliferation centers in tissue infiltrates.


How is SLL diff from CLL?

SLL is used for nonleukemic patients with the tissue morphology and immunophenotype of CLL.


Who does CLL effect?

adults in Western countries, but it is very rare in far Eastern countries.

How much percent does CLL/SLL accounts for of non-Hodgkin lymphomas (NHLs) in biopsies?

almost 7%

What is the median age onset of leukemia?

is 65 years. This form of leukemia is rare before age 20 and uncommon before age 50.


Who does leukemia effect most and by how much?


More males than females (1.5 to 2.1:1) are afflicted by the disorder.


Of all hematologic neoplasm, which BLANK has the hight genetic predisposition and by how much?

CLL has the highest genetic predisposition of all hematologic neoplasms. A family predisposition can be documented in 5% to 10% of patients with CLL. The overall risk is two to seven times greater in first-degree relatives of CLL patients.


What type of disorder is CLL?

B-cell disorder

What percent of lymphoid neoplasms worldwide do mature B-cell neoplasms comprise?

90%

What is B-CLL?

A biologically and clinically heterogeneous hematologic malignancy characterized by a gradually progressive accumulation of morphologically mature B lymphocytes in the blood, bone marrow, and lymphatic tissues.

How are B-CLL cells characterized?

As CD5+, CD19+, and CD23+ monoclonal B cells.

What is an excess of B cells likely to be a result of?

decreased apoptosis and deregulation of cell cycle control

The anti-apoptotic BCL2 gene is reported to be overexpressed in what percent of B cells?

65%-70%

CLL is heterogeneous on what levels?

Clinical, cellular, and molecular

Chromosomal alterations occur in what percent of CLL cases?

80%

What do those alterations include?

The 13q deletion, the 11q deletion, trisomy of chromosome 12, and the 17p deletion.

What does The high rate of recurrence of the same chromosomal abnormalities suggest?

That these abnormalities may affect a common pathway.

What are the two major applications in the analysis of chronic lymphoid malignancies?

Demonstration of the clonal nature of a population of lymphoid cells and Detection of pathogenetically important rearrangements, for example, clonal IG or TCR gene rearrangements, that are useful in diagnosis of CLL

Why is the IgVH mutational status important?

Important in determining the prognosis of patients with CLL

What is ZAP-70?

Zeta-chain, associated protein 70

What was recently discovered about ZAP-70?

Recently discovered to be differentially expressed in the CLL subgroup without IgVH mutation that had poor outcomes.

How is thymidine kinase significant?

A new finding has shown a correlation of the serum value of thymidine kinase with IgVH gene mutational status and also with disease progression

What is CD38?

Expression of CD38, a membrane protein that marks cellular activation and maturation and that has signaling activity

What does the expression of CD38 correlate with

the presence of IgVH mutations

How are microRNA expression profiles used?

To distinguish normal B cells from malignant B cells in CLL patients

What do microRNAs regulate?

The expression of protein-coding genes and can act as oncogenes, tumor suppressors, or both

What do alterations in CLL affect?

Evasion of apoptosis, Self-sufficiency in growth, and Stimulation of angiogenesis and dissemination.

What is evasion of apoptosis associated with?

overexpression of the antiapoptotic protein BCL2.

What is BCL2 responsible for?

maintaining the delicate homeostasis between proliferation and apoptosis and promotes cell survival by inhibiting cell death.

What does self-sufficiency in growth demonstrate?

that normal cells require growth stimuli compared to cancer cells that are capable of generating their own growth signals without having to rely on mitogens in the surrounding environment in order to actively proliferate.

What are the staging classifications?

    • 0—Bone marrow and blood lymphocytosis

    • I—Lymphocytosis with enlarged nodes

    • II—Lymphocytosis with enlarged spleen or liver or both

    • III—Lymphocytosis with anemia

IV—Lymphocytosis with thrombocytopenia

What do Parameters with demonstrated independent prognostic values include?

    • Number of lymphocytes in the peripheral blood

    • Degree of bone marrow infiltration

    • Proportion of abnormal lymphoid cells in the peripheral blood

    • Lymphocyte doubling time

    • Immunoglobulin heavy-chain variable-region gene mutation status

    • Cytogenetic abnormalities assessed by fluorescent in situ hybridization

    • Z-chain–associated protein kinase-70 protein expression

How is CLL usually discovered and why?

    • At the time of a routine physical exam because it is asymptomatic

Findings on what test typically suggest that the disease is present?

    • On a CBC

Excess lymphoid production crowds out what elements?

    • Normal bone marrow

How?

    • By packing of the bone marrow space by malignant lymphocytes.

What does this result in?

    • Anemia, thrombocytopenia, and neutropenia

What is the range for total leukocyte counts?

    • Total leukocyte counts can range from 30 to 200 x 109/L

What percentage of small lymphocytes are exhibited in peripheral blood smears with Chronic Lymphocytic Leukemia (CLL)?



80-90%

Why are many of the cells in peripheral blood smears look overly mature in Chronic Lymphotic Leukemia Patients?

Because they have hypercondensed nuclear chromatin pattern.

What are typically seen in peripheral blood smears of CLL Patients?

Smudge Cells.

In peripheral blood smears of CLL patients, what are normal levels?

Granulocytes and Platelets

What is hyper leukocytosis?

An elevated leukocyte concentration in a centrigued peripheral blood specimen from a patient with T-cell acute lymphoblastic leukemia


What are curative and non-curative treatment options for CLL patients?

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell CLL.
chemoimmunotherapy is an non-curative treatment that incorporates the use of monoclonal antibodies to chemotherapy.

How does one asses minimal residual disease in CLL patients?


Real time PCR and Flow Cytometry based assays.

How is Hairy Cell Leukemia (HCL) diagnosed?

Hairy Cell Leukemia is a mature B-cell malignancy that is diagnosed based on clinical features, morphology, and phenotyping.

Which sex is HCL much more common to occur, and why ?


It is much more common in females due to a possible involvement with the X chromosome.

What age does HCL usually occur?


HCL usually occurs after 30 years of age.

How did Hairy Cell Leukemia got its name?


HCL is so named because of the appearance of fine, hair-like, irregular cytoplasmic projections that are characteristic of lymphocytes in this disease.


Which organs do Prolymphocytic Leukemia usually affect?



B-cell Prolymphocytic Leukemia represents a malignancy of B prolymphocytes affecting blood, bone marrow, and spleen.

How is Prolymphocytic Leukemia characterized?

Prolymphocytic leukemia is characterized by a large number of small lymphocytes with scant cytoplasm and the immature features of prolymphocytes in the peripheral blood.


In Prolymphocytic Leukemia Leukocytes and Prolymphocytes can exceed to?

100 × 109/L for Leukocytes and Prolymphocytes must exceed 55% of lymphoid cells in the peripheral blood.


What are plasma cell neoplasms?

Multiple Myeloma and Waldenström primary macroglobulinemia


What is multiple myeloma?

Multiple myeloma is a malignant bone marrow–based plasma cell neoplasm associated with abnormal protein production.


How much does multiple myeloma account for in all malignancies and all hematological malignancies?

Multiple myeloma accounts for approximately 1% of all types of malignant diseases and about 10% of hematological malignancies.


What is present in 2/3 of patients with multiple myeloma?


Anemia is present at the time of diagnosis in approximately two thirds of patients.


What happens in rare terminal cases of multiple myeloma?

In rare cases in the terminal stages, plasmablasts and plasma cells may amount to 50% of the leukocytes in the peripheral blood. Rouleaux formation on peripheral blood smears is common.


What is the leukocyte and lymphocyte count look like with multiple myeloma?

The leukocyte count can be normal, although about one third of patients have leukopenia. Relative lymphocytosis is usually present. Sometimes, eosinophilia is noted.


How do the platelets look like for patients with multiple myeloma?

Platelet abnormalities, impaired aggregation of platelets, and interference with platelet function by the abnormal monoclonal protein contribute to bleeding.


Why is bleeding common in multiple myeloma?


Bleeding is common due to inhibition of coagulation factors and thrombocytopenia from marrow infiltration of plasma cells or chemotherapy.


What coagulation factors are increased during multiple myeloma?


Fibrinogen and Factor VIII

What does electrophoresis of serum from myeloma patients reveal?

Increased IgM production, IgG, and less frequently IgA. Increased production of IgD is rarely seen.

What are current treatments for multiple myeloma?


Thalidomide, lenalidomide, and bortezomib are used for newly diagnosed patents. Chemotherapy cannot cure multiple myeloma


Waldenström Primary Macroglobulinemia usually appear in what sex, age-range, and race?


Usually found in older men. The median age of onset varies between 63 and 68 years of age and the incidence of is higher among whites.

What are the prognostic factors for Waldenström Primary Macroglobulinemia patients?

Prognostic factors include the patient’s age, β2-microglobulin level, monoclonal protein level, hemoglobin concentration, and platelet count.


What is the reported median survival for patients with Waldenström Primary Macroglobulinemia.

The reported median survival of patients with WM ranges between 5 and 10 years from the time of diagnosis.


How is Waldenström Primary Macroglobulinemia characterized?

WM is a B-cell neoplasm characterized by lymphoplasma proliferative disorder with infiltration of the bone marrow and a monoclonal immunoglobulin M (IgM) protein.


What is the most consistent feature of the bone marrow and lymph nodes of Waldenström Primary Macroglobulinemia patients?


It’s the presence of pleomorphic B-lineage cells at different stages of maturation.

What is the viscosity of the samples of patients with Waldenström Primary Macroglobulinemia?


Blood samples of patients with Waldenström Primary Macroglobulinemia exhibit hyperviscosity.

How does one detect monoclonal gammopahties in patients with Waldenström Primary Macroglobulinemia?


serum protein electrophoresis (SPEP) and immunoelectrophoresis (IFE)

What are the cryoglobulins in Waldenström Primary Macroglobulinemia samples ?


IgM and IgG

What is the solid tumor counterpart of stem cell leukemia?


Undifferentiated Lymphoma.

What is the solid tumor counterpart of monocytic leukemia?

Reticulum cell sarcoma.

What is the relationship between Lymphomas and Leukemias?

he neoplastic cells of these two disorders are identical.

What are some characteristics of Lymphomas?

Are a group of closely related disorders that characterized by the overproliferation of one or more type of cells of the lymphoid system such as lymphoreticular stem cells, lymphocytes, reticulum cells, and histiocytes.

What is Malignant Lymphoma?

Malignant Lymphoma expresses itself as a disorder of the lymph nodes.

What is Myeloid System?

Immature white blood cells for example, blast, pro, myelo, meta, reticular, band, and mature white blood cells.

What is the Lymphoid

Are B-cells and T-cells

What are two major forms of Malignant Lymphomas?

Hodgkin and Non-Hodgkin (NHL)

What is NHL?

Non-Hodgkin Lymphoma (NHL) account for more than two thirds of lymphomas and more than 75% of fatalities due to lymphoma.

What is a rare forms of Lymphoma?

A rare forms of lymphoma include Burkitt lymphoma

And mycosis fungoides, a variant of Sezary syndrome, which



Demonstrates skin involvement.

What is Pathophysiology?

  • Although the etiology of most lymphomas is unknown, the potential role of a virus in the pathogenesis of lymphomas is strongly suspected.

  • In humans, the development of B cells in the bone marrow is initiated by the assembly of genes for the variable regions of the heavy and light chains of antibodies in B-cell progenitors, mediated by a process called V(D)J recombination.

In this process, the DNA located between the rearranging gene elements is deleted from the chromosome (or sometimes inverted).

What is Etiology?

  • cause of diseases

What is Pathogenesis?

  • The origin of disease

What is Hodgkin Disease?

  • Cytogenetic studies now suggest that Reed-Sternberg cells arise from a single clone, a common B-cell precursor located in a germinal center.

What are Reed-Sternberg Cells?

  • Reed-Sternberg cells are a defining feature of Hodgkin disease, but less than 1% of cells in a sample of Hodgkin disease tissue are Reed-Sternberg Cells.

What is Non-Hodgkin Lymphoma (NHL)?

  • The most frequent type of NHL is diffuse large B-cell lymphoma, which accounts for approximately 40% of new cases of lymphoma.

  • More than half of patients with diffuse large B-cell lymphoma are older than 60 years of age.

What are the characteristics of NHL?

  1. In NHL, Reed-Sternberg cells are absent. The infiltrating cells may be of one type or may have a mixed cell population of lymphocytes, histiocytes, eosinophils, and some plasma cells.

What is cytogenetic analysis?

  1. The chromosomal anomalies that have been observed in hematological malignant disease include structural rearrangement as translocations and deletions and numerical abnormalities with respect to structural rearrangements.

What is Sézary Syndrome?

  1. The leukemic phase of cutaneous T-cell lymphoma, mycosis fungoides, is called Sézary syndrome.

What was the Ph1 chromosome?

It was the first aberrant chromosome described in a malignant disorder.

The majority of Ph1-positive patients have the typical t(9;22) translations.



What is the abl gene product ?

A protein tyrosine kinase, and the fusion protein bcr-abl has constitutive kinase activity that deregulates signal transduction pathways, causing abnormal cell cycling, inhibition of apoptosis, and increased proliferation of cells.

What CML is the best characterized leukemia at?

A molecular level.

What express patients with CML and acute lymphoblastic leukemia?

The BCR gene rearrangement¾the molecular counterpart of the Ph1 chromosome.

What oncogene is activation by?

Chromosomal translocation.

Chronic myelogenous leukemia.

Breaks at the ends of the long arms of chromosomes 9 and 22 allow reciprocal translocations to occur. The c-abl protooncogene on chromosome 9 is translocated to the breakpoint region (bcr) of chromosome 22. The result is the Philadelphia chromosome, which contains a new fusion gene coding for a hybrid oncogenic protein (bcr-abl), presumably involved in the pathogenesis of chronic myelogenous leukemia

What reason is detecting gene rearrangements involving the BCR and C-ABL genes?

    • Confirmation of Ph1-positive cases of CML

    • Diagnosis of Ph1-negative cases of CML

    • Diagnosis of CML presenting in blast crisis

    • Monitoring of patients with CML during and after therapy for the detection of minimal residual disease

    • Confirmation of remission

    • Early detection of relapse




Which the clinical course of CML can be characterized by three separate progressive phases?

  • Initial phase

  • Accelerated phase

    1. Blast crisis (acute)

What is Initial phase?

  1. Onset of the early, initial phase (chronic phase) of CML is insidious and may last for 3 to 5 years. Most cases (85%) are diagnosed in this phase.

What is Accelerated phase?

  1. Transitional, accelerated period may precede blast transformation. This transition is heralded by a rising peripheral blood leukocyte count, an increased percentage of basophils, worsening anemia, and thrombocytopenia.

What is blast crisis (acute)

  1. it is characterized by the appearance of primitive blast cells similar to those seen in acute leukemia

What is Myeloproliferative neoplasms (MPNs)?

They are interrelated clonal hematopoietic stem cell disorders characterized by excessive proliferation of one or more mature myeloid cell lines, for example, granulocytes, erythrocytes, megakaryocytes, or mast cells.

What distinguishes MPNs from other neoplasms?

The discovery of mutations in crucial genes

What is now being incorporated into the diagnostic workup of MPNs?


Molecular analysis

What are one or more shared features of the multipotent hematopoietic stem cells (CD 34) in MPNs

1) Cytogenetic abnormalities

2) Overproduction of one or more types of blood cells with dominance of a transformed clone

3) Hypercellular marrow or marrow fibrosis

4) Thrombotic and/or hemorrhagic bleeding

5) Extramedullary hematopoiesis

6) Transformation to acute leukemia



Which of the following MPNs characteristics is also known as agnogenic myeloid metaplasia or myelofibrosis with myeloid metaplasia ?
1. Choronic myelogenous leukemia (CML)

2. Polycythemia rubra vera

3. Primary myelofibrosis

4. Essential thrombocythemia





Primary myelofibrosis

2008 who classification of myeloid Neoplasms ?

Tyrosine kinase mutation

Janus kinase mutation



What is the primarily neoplasms age of MPNs in adults ?

50 to 70

What is the spent phase found in myeloproliferative disorder ?

It is the halting of all blood cell production in the marrow and the increase in fibrosis

What condition do myeloproliferative disorders transform to ?

Acute leukemia

A mutation in Jak2 is associated with which types of myeoloproliferative conditions?

Polycythemia vera, essential thrombocythemia,

Primary myeolfibrosis



Is maturation in –tact in myeloprolife rative disorder?

Yes there is effective maturation leading to increased peripheral blood counts

Descrive chronic myelogenous leukemia (CML)

Is an MPN that originates in an abnormal pluripotent bone marrow stem cell and is consistently associated with the BCR –ABL 1 fusion gene located in the Philadelphia chromosome

What are the other principal types of chronic leukemia ?

CML and chronic lymphocytic leukemia

What two genes are commonly mutated in primary myelofibrosis?

Activating JAK2 mutations and MPL

True or false ? CML is a clonal proliferative disorder of the pluripotent hematopoietic progenitor cell that resulrs in a disordered proliferation of cells

True

What is CML characterized by ?

Chronic, indolent disease course that frequently transforms into a terminal, acute blast crisis phase

Excessive increase in mostly mature myeloid cell in peripheral blood id the ________ of the intioal (chronic) phase of CML

Hallmark

what is the median age of diagnoses for chronic Myelogenous Leukemia ?

50-60

True or false in CML males a slightly greater rate of disease occurrence?

True

What causes unregulated cell overproduction in chronic Myelogenous leukemia ?

Increased tyrosine kinase activity

What is the name of the chromosome that originates in an abnormal pluripotent bone marrow stem cell and is consistently associated with the BCR-ABL 1 fusion gene ?

Philadelphia chromosome

What are the clinical fetures of chronic myelogenous leukemia ?

Fatigue

Approximately ________of patients whose illness transforms into acute leukemia develop myelogenous leukemia

Two thirds

What are some diagnostic coagulation abnormalities ?

Prolonged activated partial thromboplastin time (APTT) and significantly decreased level of factor V

During allogeneic bone marrow transplantation, what is induced by high-dose chemoradiotherapy?

Myeloablation


Describe alloimmune graft versus leukemia (GvL) effect?


Mediated by donor T-lymphocytes

What is crucial for identifying disease stage and progression as well as response to therapy?


Patient monitoring at the cytogenetic and molecular levels

Patients who achieve complete marrow cytogenetic remission should still be checked at __(a)_____ and in the face of ___(b)___.

  1. Intervals

Rising blood bcr-abl transcript levels.

Polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PM) are what?


  1. Clonal disorders of multipotent hematopoietic progenitors.

Polycythemia Rubra Vera is?

A primary disorder characterized by extremely increased red cell mass.



What is the number of incidences PV effect?

2.3 per 100,000 people

What is the median age at which PV is diagnosis?

60 years old

What gender does PV primarily effect?

Male

What seems to increase the risk of PV?


Exposure to radiation, benzene, and petroleum refineries

PV is a clonal hematopoietic progenitor cell disorder with?



Trilineage hyperplasia; the most constant and striking feature is erythroid hyperplasia of the bone marrow.

A very slow evolution of the malignant erythroid clone leads to what?

Overexpansion of the red cell mass, hypervolemia, and splenomegalic red cell pooling.

What gene has been described in neutrophils of patients with PV?

PV-1 gene

True or False: Plethora is the hallmark of PV?

TRUE

Which disease occurs in more than 75% of patients?

Splenomegaly

True or False: Irreversible, moderate hypertension rarely occurs as the result of the expanded blood volume.

FALSE

Which percentage of patients report neurological symptoms?

50% to 80%

What are complications of Polycythemia Rubra Vera (PV)?

Thrombosis and paradoxical hemorrhage

Characteristics of PV are:

Increased erythrocyte cell count, packed cell volume

and hemoglobin with normal erythrocytic indices



What is the treatment for PV?

Therapeutic phlebotomy, drug therapy

What is the median survival time for untreated symptomatic patients after diagnosis?

6 to 18 months

What is the median survival time with treatment?

More than 10 years

Which disorder is characterized by systemic bone marrow fibrosis and extramedullary hematopoiesis?

Primary myelofibrosis

What characterizes secondary myelofibrosis?

Infiltrative disorders, including malignancies and infections, or exposure to chemical toxins or irradiation.

True or False: Primary myelofibrosis is uncommon

TRUE

About what percentage of patients with PV develop myelofibrosis?

20.00%

What happens to patients with myelofibrosis?

They may undergo temporary or permanent transition to PV or may convert to CML.

What is primary myelofibrosis

Primary myelofibrosis is a clonal disorder of the multipotential progenitor cell compartment.

Dysmegakaryocytopoiesis leading to an overproduction of defective platelets is the most constant feature of myelofibrosis.




What is the % of patients acquired recurrent cytogenetic abnormalities?

Approximately 40% of patients acquire recurrent cytogenetic abnormalities and nearly 80% acquire nonspecific aberrations.

What are the clinical signs and symptoms of myelofibrosis?

Patients with myelofibrosis usually exhibit progressive anemia, splenomegaly, and marrow fibrosis.

Explain the cellular alterations in myelofibrosis

The leukoerythroblastic picture of teardrop-shaped erythrocytes, nucleated erythrocytes, and immature myeloid cells is classic for myelofibrosis.

Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow are characteristic in the early stages.

Extramedullary hematopoiesis, peripheral cytopenias, and myelofibrosis reflect the changes seen in the later stages.

Transitions among the different types of MPNs and termination in acute leukemia or marrow failure are common



What have been identified as factors with prognostic significance in patients with primary myelofibrosis ?

hemoglobin concentration, platelet count, and the presence of osteomyelosclerosis

What is the median survival time ranges?

The median survival time ranges from 4.3 to 5.0 years.

What are some of the treatments of myelofibrosis?

Treatment of myelofibrosis can consist of periodic transfusions of packed red blood cells, androgens, cytotoxic agents, and platelet reduction by plateletpheresis.

Describe Essential or primary thrombocythemia and the causes

Essential or primary thrombocythemia is characterized by a significant increase in circulating platelets, usually in excess of 1,000 x 109/L.

Elevated platelet counts may be encountered as a reactive phenomenon, secondary to a variety of systemic conditions, or they may represent essential thrombocythemia, a primary disorder of the bone marrow.



What is a usual lab finding when dealing with essential thrombocythemia?

Significantly elevated peripheral blood platelet count, usually in excess of 1,000 x 109/L, with a minimum of 600 x 109/L

How are peripheral blood erythrocytes frequently described as during essential thrombocythemia?

Hypochromic and microcytic

If splenic atrophy is present, during essential thrombocythemia, abnormal morphology includes:

  • Target cells

  • Howell-Jolly bodies

  • Nucleated erythrocytes

Acanthocytes

In more than half of patients with thrombocythemia, the platelet-rich plasma does not respond to epinephrine.

  1. Epinephrine

By what characteristic can thrombocythemia and polycythemia vera be differentiated?

  1. The absence of an expanded red blood cell mass in thrombocythemia.

The chronic leukemias are usually characterized by the presence of what?

leukocytosis

The total leukocyte count is usually greater than what amount?

50x109/L and may exceed 300 x 109/L.


Peripheral blood smears demonstrate increased numbers of mature granulocytic forms. What type of granulocytic forms are observed?

segmented neutrophils and band forms, and smaller numbers of immature forms.

Cytochemical studies are used less frequently for chronic leukemias than for what other type of leukemia?

acute leukemias.

In special cases, leukocyte alkaline phosphatase (LAP) procedure is used to differentiate between CML and what other type of reaction?

a leukemoid reaction

In CML, the LAP score is (decreased or increased )as compared with a leukemoid reaction, in which a high score is usual.

decreased

Because chronic-phase CML is highly responsive to treatment, many patients experience at least how many remissions?


one

Remissions can last from several weeks to months, with 60% of patients becoming what?

asymptomatic

The introduction of imatinib has fundamentally altered the management of patients with CML in what phase?

Chronic phase

It is recommended as the best single agent for newly diagnosed patients who are not eligible for initial treatment by allogeneic what type of cell transplantation?

Stem cell

A long-standing and universally accepted therapy for CML is allogeneic stem cell transplantation (allo-SCT). Allo-SCT achieves its curative potential via at least how many mechanisms?

Two

How is Myelodysplastic Syndrome (MDS) characterized?

MDS is characterized by the simultaneous proliferation and apoptosis of hemopoietic cells that lead to a normal or hypercellular bone marrow biopsy and peripheral blood cytopenia.

What is included in the classification Myelodysplastic/Myeloproliferative Neoplasm (MDS/MPN)?

Clonal myeloid neoplasms that at initial presentation have some clinical, laboratory, or morphologic findings that support a diagnosis of MDS and other findings that are more consistent with MPN.

What is usually demonstrated in patients placed in the MDS/MPN category, as in chronic myelomonocytic (CMML)?

Hypercellular bone marrow because of proliferation of one or more cell lines

The MDSs and MDSs/MPNs are a heterogeneous group of clonal disorders of what?

Bone marrow

True or False

The clonal nature of MDS is supported by research studies, even in the absence of detectable cytogenetic abnormalities.



True

True or False

The MDSs are classified into various types of refractory anemias, one of the included subtypes is Refractory anemia with excess of sideroblasts (RAEB-1 and RAEB-2)



False (Refractory anemia with excess of blasts (RAEB-1 and RAEB-2)

What occurs without a known history of chemotherapy or radiation exposure?

Primary or de novo MDS

___________MDS can sometimes be directly related to a known agent.

Secondary

What are the risk factors may be possible etiologies for developing MDS?

Age, Genetic predisposition, Environmental exposure, prior therapy, other factors( eg. Abuse of drugs, OTC drugs)

Exposure particularly with benzene and possibly other industrial solvents may be a possible etiology for developing what syndrome?

Myelodysplastic Syndromes

Fanconi anemia, Shwachman-Diamond syndrome, and Diamond-Blackfan syndrome are associated with an increased risk of what syndrome?

Myelodysplastic Syndromes

True or false

MDS is rare in adult.



False (rare in childhood)

MDS is more common in males or females?

Males

True or False

The adult form usually occurs in persons older than 50 years of age (most patients are 60 to 75 years old).



True

What chromosomes are mainly involved in characteristic karyotype anomalies?

Chromosomes 5, 7, and 8.

Survival of patients with MDS is better for those with what chromosomal patters?

Normal chromosomal patterns

What are the clinical signs and symptoms that maybe reported by a patient with MDS?

History of infections, bleeding, weight loss, or cardiovascular symptoms may be reported by a patient

In MDS, what causes the infections?

Infections are caused by dysfunctional granulocytic neutrophils or absolute granulocytopenia.

Dysfunctional granulocytic neutrophils or absolute granulocytopenia causes what?

Infections

What causes the hemorrhages that occurs in patients with MDS?

Decreased or dysfunctional platelets

What is the common initial presenting symptom in MDS?

Anemia

Laboratory manifestations of MDS include________,________, and _________.

  1. Anemia

  2. Low platelet count

  3. Low total leukocyte count

  4. All of the above

D

Another MDS laboratory manifestation includes____________.

  1. Poikilocytosis

  2. Microcytic anemia

  3. Macrocytic anemia

  4. Absolute Nuetropenia

D

Peripheral blood smears _________ exhibit red blood cell abnormalities and large dysfunctional platelets in MDS.

a. rarely

b. frequently

c. mostly



d. always




RA is one of the refractory cytopenias with___________ dysplasia, is the mildest form of all types of MDS. Fill in the blank.

  1. Unilineage

  2. Multilineage

  3. Omnilineage

  4. monolineage

A

RARS has the presence of sideroblasts. True or False

False, it has ringed siderblasts

RAEB-1 and RAEB-2 have the presence of type 1 and Type 2 myeloblasts in bone marrow and in blood. Tue or False

True

Chronic myelomonocytic leukemia (CMML) is a ________ hematologic malignancy that is characterized by features of both an MPN and an MDS.

  1. Polyclonal

  2. Monoclonal

  3. Clonal

  4. Uniclonal

C

CMML is less frequent than the _______ variety.

  1. Chronic

  2. Acute

  3. Malefic

  4. Asymptomatic

B

In the Diagnosis of CMML, according to the FAB classification criteria, distinguishes between two forms, CMML-1 and CMML-2. True or False


True

The hallmark of CMML are Peripheral blood smears usually demonstrate a persistent monocyte count greater than 1 × 109/L. True or False

True

CMML does not include Nuetrophilia as a commonly observed hallmark. True or False

False

One of the most widely used prognostic systems for MDS patients is the International Prognostic Scoring System (IPSS). A score of more than or equal to 2.5 is considered high risk. True or False

True





Share with your friends:
1   2


The database is protected by copyright ©dentisty.org 2019
send message

    Main page