White Blood Cell Disorders Flashcards
1
Q
Basic Principles
A
- hematopoiesis occurs in a stepwise maturation of CD34+ hematopoietic stem cells
- cells mature and are released from the bone marrow into the blood
- a normal WBC count is approximately 5-10 K/mL
- low WBC is called leukopenia (10)
2
Q
Leukopenia (neutropenia)
A
- neutropenia refers to a decreased number of circulating neutrophils
- drug toxicity: damage to stem cells results in decreased production of WBCs, especially neutrophils
- severe infection: increased movement of neutrophils into tissues results in decreased circulating neutrophils
- as a treatment, GM-CSF or G-CSF may be used to boost granulocyte production, thereby decreasing risk of infection in neutropenic pts
3
Q
Leukopenia (lymphopenia)
A
- refers to a decreased number of circulating lymphocytes
- immunodeficiency: (e.g. DiGeorge syndrome or HIV)
- high cortisol state (e.g. exogenous corticosteroids or Cushing syndrome): induces apoptosis of lymphocytes
- autoimmune destruction (e.g. systemic lupus erythematosus)
- whole body radiation: lymphocytes are highly sensitive to radiation; lymphopenia is the earliest change to emerge after whole body radiation
4
Q
Neutrophilic Leukocytosis
A
- refers to increased circulating neutrophils
- bacterial infection or tissue necrosis: induces release of marginated pool and bone marrow neutrophils, including immature forms (left shift); immature cells are characterized by decreased Fc receptors (CD16)
- high cortisol state: impairs leukocyte adhesion, leading to release of marginated pool of neutrophils
5
Q
Monocytosis
A
- refers to increased circulating monocytes
- causes include chronic inflammatory states (e.g. autoimmune and infectious) and malignancy
6
Q
Eosinophilia
A
- refers to increased circulating eosinophils
- causes include allergic reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma
- eosinophilia is driven by increased eosinophil chemotactic factor
7
Q
Basophilia
A
- refers to increased circulating basophils
- classically seen in chronic myeloid leukemia
8
Q
Lymphocytic Leukocytosis
A
- refers to increased circulating lymphocytes
- viral infections: T lymphocytes undergo hyperplasia in response to virally infected cells
- Bordetella pertussis infection: bacteria produce lymphocytosis-promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph nodes
9
Q
Infectious Mononucleosis (IM)
A
- EBV infection that results in a lymphocytic leukocytosis comprised of reacive CD8+ T cells
- CMV is a less common cause
- primarily infects oropharynx, resulting in pharyngitis; liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes; B cells
- CD8+ T cell response leads to generalized lymphadenopathy due to T-cell hyperplasia in the lymph nodes; splenomegaly due to T-cell hyperplasia in the pariarterial lymphatic sheath (PALS); high WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood
10
Q
Monospot Test for Mononucleosis
A
- detects IgM antibodies that cross-react with horse or sheep red blood cells (heterophile antibodies)
- usually turns positive within 1 week after infection
- a negative monospot test suggests CMV as a possible cause of IM
- definitive diagnosis is made by serologic testing for the EBV viral capsid antigen
11
Q
Complications of Mononucleosis
A
- increased risk for splenic rupture; patients are generally advised to avoid contact sports for 1 month
- rash if exposed to ampicillin
- dormancy of virus in B cells leads to increased risk for both recurrence and B-cell lymphoma, especially if immunodeficiency (e.g. HIV) develops
12
Q
Acute Leukemia (Basic Principles)
A
- neoplastic proliferation of blasts; defined as the accumulation of >20% blasts in the bone marrow
- increased blasts “crowd-out” normal hematopoiesis, resulting in an “acute” presentation with anemia (fatigue), thrombocytopenia (bleeding), or neutropenia (infection)
- blasts usually enter the blood stream, resulting in high WBC count
- blasts are large, immature cells, often with punched out nucleoli
- acute leukemia is subdivided into acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) based on the phenotype of the blasts
13
Q
Acute Lymphoblastic Leukemia (ALL)
A
- neoplastic accumulation of lymphoblasts (>20%) in the bone marrow
- lymphoblasts are characterized by positive nuclear staining for TdT, a DNA polymerase
- TdT is absent in myeloid blasts and mature lymphocytes
- most commonly arises in children; associated with Down syndrome (usually arises after the age of 5 years)
- subclassified into B-ALL and T-ALL base don surface markers
14
Q
B-ALL
A
- most common type of ALL
- usually characterized by lymphoblasts (TdT+) that express CD10, CD19, and CD20
- excellent response to chemotherapy; requires prophylaxis to scrotum and CSF
- prognosis is based on cytogenetic abnormalities
- t(12;21) has a good prognosis; more commonly seen in children
- t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+ALL)
15
Q
T-ALL
A
- characterized by lymphoblasts (TdT+) that express markers ranging from CD2 to CD8 (e.g. CD3, CD4, CD7)
- the blasts do not express CD10
- usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)
16
Q
Acute Myeloid Leukemia
A
- neoplastic accumulation of immature myeloid cells (>20%) in the bone marrow
- myeloblasts are usually characterized by positive cytoplasmic staining for myeloperoxidase (MPO)
- most commonly arises in older adults (avg 50-60 yrs)
- subclassification based on cytogenetic abnormalities, lineage of immature myeloid cells, and surface markers
- AML may also arise from pre-existing dysplasia (myelodysplastic syndromes), especially with prior exposure to alkylating agents or radiotherapy
- myelodysplastic syndromes usually present with cytopenias, hypercellular bone marrow, abnormal maturation of cells, and increased blasts (<20%)
- most patients die from infection or bleeding, though some progress to acute leukemia
17
Q
Acute Promyelocytic Leukemia (APL)
A
- characterized by t(15:17), which involves translocation of the retinoic acid receptor (RAR) on chromosome 17 to chromosome 15; RAR disruption blocks maturation and promyelocytes (blasts) accumulate
- abnormal promyelocytes contain numerous primary granules that increase the risk for DIC
- treatment is with all-trans-retinoic acid (ATRA, a vitamin A derivative), which binds the altered receptor and causes the blasts to mature (and eventually die)
18
Q
Acute Monocytic Leukemia
A
- proliferation of monoblasts; usually lack MPO
- blasts characterstically infiltrate gums
19
Q
Acute Megakaryoblastic Leukemia
A
- proliferation of megakaryoblasts; lack MPO
- associated with Down syndrome (usually arises before the age of 5)
20
Q
Chronic Leukemia (Basic Principles)
A
- neoplastic proliferation of mature circulating lymphocytes; characterized by a high WBC count
- usually insidious in onset and seen in older adults
21
Q
Chronic Lymphocytic Leukemia (CLL)
A
- neoplastic proliferation of naive B cells that co-express CD5 and CD20
- increased lymphocytes and smudge cells are seen on blood smear
- involvement of lymph nodes leads to generalized lymphadenopathy and is called small lymphocytic lymphoma
22
Q
Complications of CLL
A
- hypogammaglobulinemia: infection is the most common cause of death in CLL
- autoimmune hemolytic anemia
- transformation to diffuse large B-cell lymphoma (Richter transformation) - marked clinically by an enlarging lymph node or spleen
23
Q
Hairy Cell Leukemia
A
- neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes
- cells are positive for tartrate-resistant acid phosphatase (TRAP)
- clinical features include splenomegaly (due to accumulation of hairy cells in red pulp) and “dry tap” on bone marrow aspiration (due to marrow fibrosis)
- lymphadenopathy is usually absent
- excellent response to 2-CDA (cladribine), an adenosine deaminase inhibitor; adenosine accumulates to toxic levels in neoplastic B cells
